Compounds to treat alzheimer&#39;s disease

ABSTRACT

The present invention is substituted amines of formula (X)  
                 
 
     and of the formula (X′)  
                 
 
     useful in treating Alzheimer&#39;s disease and other similar diseases.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to the following provisionalapplications: U.S. provisional application Serial No. 60/215,323, filedJun. 30, 2000; U.S. provisional application Serial No. 60/252,736, filedNov. 22, 2000; U.S. provisional application Serial No. 60/255,956, filedDec. 15, 2000; U.S. provisional application Serial No. 60/268,497, filedFeb. 13, 2001; U.S. provisional application Serial No. 60/279,779, filedMar. 29, 2001; and U.S. provisional application Serial No. 60/295,589,filed Jun. 4, 2001.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention is directed to compounds useful intreatment of Alzheimer's disease and similar diseases.

[0004] 2. Description of the Related Art

[0005] Alzheimer's disease (AD) is a progressive degenerative disease ofthe brain primarily associated with aging. Clinical presentation of ADis characterized by loss of memory, cognition, reasoning, judgement, andorientation. As the disease progresses, motor, sensory, and linguisticabilities are also affected until there is global impairment of multiplecognitive functions. These cognitive losses occur gradually, buttypically lead to severe impairment and eventual death in the range offour to twelve years.

[0006] Alzheimer's disease is characterized by two major pathologicobservations in the brain: neurofibrillary tangles and beta amyloid (orneuritic) plaques, comprised predominantly of an aggregate of a peptidefragment know as A beta. Individuals with AD exhibit characteristicbeta-amyloid deposits in the brain (beta amyloid plaques) and incerebral blood vessels (beta amyloid angiopathy) as well asneurofibrillary tangles. Neurofibrillary tangles occur not only inAlzheimer's disease but also in other dementia-inducing disorders. Onautopsy, large numbers of these lesions are generally found in areas ofthe human brain important for memory and cognition.

[0007] Smaller numbers of these lesions in a more restricted anatomicaldistribution are found in the brains of most aged humans who do not haveclinical AD. Amyloidogenic plaques and vascular amyloid angiopathy alsocharacterize the brains of individuals with Trisomy 21 (Down'sSyndrome), Hereditary Cerebral Hemorrhage with Amyloidosis of theDutch-Type (HCHWA-D), and other neurogenerative disorders. Beta-amyloidis a defining feature of AD, now believed to be a causative precursor orfactor in the development of the disease. Deposition of A beta in areasof the brain responsible for cognitive activities is a major factor inthe development of AD. Beta-amyloid plaques are predominantly composedof amyloid beta peptide (A beta, also sometimes designated betaA4). Abeta peptide is derived by proteolysis of the amyloid precursor protein(APP) and is comprised of 39-42 amino acids. Several proteases calledsecretases are involved in the processing of APP.

[0008] Cleavage of APP at the N-terminus of the A-beta peptide bybeta-secretase and at the C-terminus by one or more gamma-secretasesconstitutes the beta-amyloidogenic pathway, i.e. the pathway by which Abeta is formed. Cleavage of APP by alpha-secretase produces alpha-sAPP,a secreted form of APP that does not result in beta-amyloid plaqueformation. This alternate pathway precludes the formation of A betapeptide. A description of the proteolytic processing fragments of APP isfound, for example, in U.S. Pat. Nos. 5,441,870; 5,721,130; and5,942,400.

[0009] An aspartyl protease has been identified as the enzymeresponsible for processing of APP at the beta-secretase cleavage site.The beta-secretase enzyme has been disclosed using varied nomenclature,including BACE, Asp, and Memapsin. See, for example, Sinha et.al., 1999,Nature 402:537-554 (p501) and published PCT application WO00/17369.

[0010] Several lines of evidence indicate that progressive cerebraldeposition of beta-amyloid peptide (A beta) plays a seminal role in thepathogenesis of AD and can precede cognitive symptoms by years ordecades. See, for example, Selkoe, 1991, Neuron 6:487. Release of A betafrom neuronal cells grown in culture and the presence of A beta incerebrospinal fluid (CSF) of both normal individuals and AD patients hasbeen demonstrated. See, for example, Seubert et al., 1992, Nature359:325-327.

[0011] It has been proposed that A beta peptide accumulates as a resultof APP processing by beta-secretase, thus inhibition of this enzyme'sactivity is desirable for the treatement of AD. In vivo processing ofAPP at the beta-secretase cleavage site is thought to be a rate-limitingstep in A beta production, and is thus a therapeutic target for thetreatment of AD. See for example, Sabbagh, M., et al., 1997, Alz. Dis.Rev. 3, 1-19.

[0012] BACE1 knockout mice fail to produce A beta, and present a normalphenotype. When crossed with transgenic mice that overexpress APP, theprogeny show reduced amounts of A beta in brain extracts as comparedwith control animals (Luo et. al., 2001 Nature Neuroscience 4:231-232).This evidence further supports the proposal that inhibition ofbeta-secretase activity and reduction of A beta in the brain provides atherapeutic method for the treatment of AD and other beta amyloiddisorders.

[0013] Published PCT application WO/0047618 entitled “Beta-SecretaseEnzyme Compositions and Methods” identifies the beta-secretase enzymeand methods of its use. This publication also discloses oligopeptideinhibitors that bind the enzyme's active site and are useful in affinitycolumn purification of the enzyme. In addition, WO/0077030 disclosestetrapeptide inhibitors of beta-secretase activity that are based on astatine molecule.

[0014] Various pharmaceutical agents have been proposed for thetreatment of Alzheimer's disease but without any real success. U.S. Pat.No. 5,175,281 discloses 21-aminosteroids as being useful for treatingAlzheimer's disease. U.S. Pat. No. 5,502,187 discloses bicyclicheterocyclic amnines as being useful for treating Alzheimer's disease.

[0015] U.S. Pat. Nos. 4,616,088 and 4,665,193 discloseshydroxyethylamine compounds as anti-hypertensive agents due to theirability to inhibit renin.

[0016] U.S. Pat. No. 4,636,491 discloses various tetrapeptides which areuseful as renin inhibitors.

[0017] U.S. Pat. No. 4,749,792 discloses amino compounds useful asanalgesics because of their ability to inhibit an enkephalin-degradingaminopeptidase.

[0018] U.S. Pat. No. 5,142,056 discloses peptide derivatives with aC₂-symmetric dihydroxyethylene core as retroviral protease inhibitors.

[0019] U.S. Pat. Nos. 5,461,067 and 5,753,652 disclose the synthesis ofretroviral protease inhibitors.

[0020] U.S. Pat. No. 5,475,138 and 5,631,405 disclose processes andvarious intermediates useful in the synthesis of selected proteaseinhibitors.

[0021] U.S. Pat. No. 5,502,061 discloses HIV protease inhibitorscontaining an unsaturated carbocycle or heterocycle at the C-terminus.

[0022] U.S. Pat. No. 5,545,640 discloses compounds which inhibit HIVprotease activity.

[0023] U.S. Pat. No. 5,516,784 discloses compounds active againstretroviruses, including HIV.

[0024] U.S. Pat. No. 5,602,175 discloses hydroxyethylamine compounds asretroviral protease inhibitors.

[0025] U.S. Pat. No. 5,631,405 discloses a process for the formation ofintermediates useful in the synthesis of selected protease inhibitors.

[0026] U.S. Pat. No. 5,733,882 and International Publications WO93/02057 and WO 93/17003 disclose dipeptide analogs as retroviralprotease inhibitors.

[0027] U.S. Pat. No. 5,760,076 discloses hydroxyethylamino sulfonamidecompounds as retrovirus protease inhibitors.

[0028] U.S. Pat. No. 5,807,870 discloses hydroxyethylamine compounds forthe inhibition of HIV protease.

[0029] U.S. Pat. No. 5,827,891 discloses HIV protease inhibitors.

[0030] U.S. Pat. No. 5,830,897 discloses hydroxyethylamino sulfonamidecompounds as retrovirus protease inhibitors.

[0031] U.S. Pat. No. 5,831,117 discloses a process and intermediatesuseful in retroviral protease inhibitor intermediates.

[0032] U.S. Pat. No. 5,847,169 discloses a process for preparingaminoepoxides involving the activation of the terminal hydroxyl of anaminodiol.

[0033] U.S. Pat. No. 5,849,911 discloses hydroxyethylamine HIV proteaseinhibitors which form hydrazines with one of the amino groups; thisamino group must also be alkylated.

[0034] U.S. Pat. No. 5,922,770 discloses peptide derivatives which areuseful in treating disorders resulting from a deficiency in growthhormone.

[0035] U.S. Pat. No. 6,013,658 discloses peptide derivatives which areuseful in treating disorders resulting from a deficiency in growthhormone.

[0036] U.S. Pat. No. 6,022,872 discloses hydroxyethylamino sulfonyl ureacompounds as HIV protease inhibitors.

[0037] U.S. Pat. No. 6,060,476 discloses hydroxyethylamino sulfonamidecompounds as HIV protease inhibitors.

[0038] International Publication WO 89/01488 discloses renin inhibitingpeptides with a hydroxyethylene or dihydroxyethylene isostere in the10,11-position of the renin substrate angiotensinogen.

[0039] International Publication WO92/00750 discloses retroviralprotease inhibitors.

[0040] International Publication WO 94/04492 discloses hydroxyethylamineintermediates useful for the treatment of retroviral diseases such asHIV. This disclosure also presents epoxides as intermediates for theretroviral inhibitors.

[0041] International Publication WO 95/06030 discloses epoxides,chloromethyl ketones, and alcohols prepared as intermediates for HIVprotease inhibitors, with a single protecting group on the amine andarylalkyl side chain substituted with alkyl, nitro, nitrile, alkoxy, andthioalkoxy; a preferred side chain is 4-fluorophenylmethyl.

[0042] International Publication WO98/29401 discloses a method for thepreparation of aminoepoxides from aminoaldehydes by which theaminoaldehyde continuously flows into a mixing zone containing an insitu generated halomethyl organometallic reagent.

[0043] International Publication WO98/33795 discloses non-peptideinhibitors of cathepsin D.

[0044] International Publication WO98/50342 discloses bis aminomethylcarbonyl compounds as inhibitors of cysteine and serine proteases.

[0045] International Publication WO/00/056335 discloses non-peptideinhibitors of aspartyl proteases. These compounds influence processingof the amyloid precursor protein APP.

[0046] EP 0 609 625 discloses HIV protease inhibitors with only onenoncyclized nitrogen atom.

[0047]Bioorganic & Medicinal Chemistry Letters, 5, 721-726 (1995)describes the synthesis of compounds useful for the inhibition of HIVprotease in which the C-terminal nitrogen of the hydroxyethylaminecompound is incorporated into a ring system such that a piperidine ring,with an amide substituent next to the nitrogen₁ is formed.

[0048] The hydroxyethylamine “nucleus” or isostere, which is present inthe compounds of the present invention has been employed with success inthe area of HIV protease inhibition. Many of these hydroxyethylaminecompounds are known as well as how to make them. See for example, J. Am.Chem. Soc., 93, 288-291 (1993), Tetrahedron Letters, 28(45) 5569-5572(1987), J. Med. Chem., 38(4), 581-584 (1994), Tetrahedron Letters,38(4), 619-620 (1997).

[0049] U.S. Pat. No. 5,648,511 discloses a diprotected aralkyl epoxide.

[0050] U.S. Pat. Nos. 5,482,947; 5,508,294; 5,510,349; 5,510,388;5,521,219; 5,610,190; 5,639,769; 5,760,064; and 5,965,588 disclosemonoprotected (substituted) aralkyl epoxides.

[0051]Tetrahedron Lett., 30(40),5425-5428 (1989) discloses a process inwhich doubly protected alpha-amino aldehydes are transformed into thecorresponding aminoalkyl epoxides.

[0052]J. Med. Chem., 36, 2300 (1993) discloses an azide substitutedbenzyl epoxide.

[0053]Tetrahedron Lett., 38, 3175 (1997) discloses a process for thepreparation of N-BOC protected epoxides from protected amino acidesters.

[0054]J. Med. Chem., 35, 2525 (1992) discloses hydroxyethylamineinhibitors of HIV protease.

[0055] U.S. Pat. No. 5,481,011 discloses arylalkyl amino epoxides inwhich the amino group is protected by a carbamate functionality.

[0056]Synlett, 6, 902 (2000) discloses the preparation ofalpha-chloroketones of aminoprotected-(substituted)benzyl esters.

[0057] U.S. Pat. No. 5,648,511 discloses a diprotected aralkyl alcohol.

[0058] U.S. Pat. Nos. 5,482,947; 5,508,294; 5,510,349; 5,510,388;5,521,219; 5,610,190; 5,639,769; 5,760,064; and 5,965,588 disclosemonoprotected (substituted) aralklyl alcohols.

[0059] U.S. Pat. Nos. 5,482,947; 5,508,294; 5,510,349; 5,510,388;5,521,219; 5,610,190; 5,639,769; 5,760,064; and 5,965,588 disclose aprocess for removing the protecting group of the monoprotected(substituted) aralklyl alcohols to give the free amino alcohol productas the amine salt.

[0060] U.S. Pat. No. 5,648,511 discloses the removal of the aminoprotecting group of the protected amino-alcohol (VIII) to give the freeamino-alcohol (IX).

[0061] U.S. Pat. No. 6,150,344 discloses phosphate containing compoundsuseful in treating Alzheimer's disease.

[0062] EP 652 009 A1 discloses inhibitors of aspartyl protease whichinhibit beta-amyloid peptide production in cell culture and in vivo. Thecompounds which inhibit intracellular beta-amyloid peptide productionare useful in treating Alzheimer's Disease.

[0063] WO00/69262 discloses a new beta-secretase and its use in assaysto screen for potential drug candidates against Alzheimer's disease.

[0064] WO01/00663 discloses memapsin 2 (human beta-secretase) as well ascatalytically active recombinant enzyme. In addition, a method ofidentifying inhibitors of memapsin 2, as well as two inhibitors aredisclosed. Both inhibitors that are disclosed are peptides.

[0065] WO01/00665 discloses inhibitors of memapsin 2 that are useful intreating Alzheimer's disease.

[0066] WO01/19797 discloses lactams of the formula—C—C—CO—N-lactam-W-X-Y-Z which are useful in treating Alzheimer'sdisease.

[0067] At present there are no effective treatments for halting,preventing, or reversing the progression of Alzheimer's disease.Therefore, there is an urgent need for pharmaceutical agents capable ofslowing the progression of Alzheimer's disease and/or preventing it inthe first place.

[0068] Compounds that are effective inhibitors of beta-secretase, thatinhibit beta-secretase-mediated cleavage of APP, that are effectiveinhibitors of A beta production, and/or are effective to reduce amyloidbeta deposits or plaques, are needed for the treatment and prevention ofdisease characterized by amyloid beta deposits or plaques, such as AD.

SUMMARY OF INVENTION

[0069] Disclosed is a substituted amine of formula (X)

[0070] where R₁ is:

[0071] (I) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F,—Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, -OC═O NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0072] (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl),

[0073] (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl),

[0074] (IV) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —CO≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0075] (V) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0076] (VI) —CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and whereR_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl,dihydronaphthayl, tetralinyl optionally substituted with one, two, threeor four of the following substituents on the aryl ring:

[0077] (A) C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above, —C≡N, —CF₃, C₁-C₃ alkoxy,

[0078] (B) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0079] (C) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0080] (D) —F, Cl, —Br and —I,

[0081] (F) —C₁-C₆ alkoxy optionally substituted with one, two or three—F,

[0082] (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedbelow,

[0083] (H) —OH,

[0084] (I) —C≡N,

[0085] (J) C₃-C₇ cycloalkyl, optionally substituted with one, two orthree substituents selected from the group consisting of —F, —Cl, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl,

[0086] (K) —CO—(C₁-C₄ alkyl),

[0087] (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0088] (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0089] (N) —SO₂—(C₁-C₄ alkyl),

[0090] (VII) —CH₂)_(n-1)(R_(1-heteroaryl)) where n₁ is as defined aboveand where R_(1-heteroaryl) is selected from the group consisting of:

[0091] pyridinyl,

[0092] pyrimidinyl,

[0093] quinolinyl,

[0094] benzothienyl,

[0095] indolyl,

[0096] indolinyl,

[0097] pryidazinyl,

[0098] pyrazinyl,

[0099] isoindolyl,

[0100] isoquinolyl,

[0101] quinazolinyl,

[0102] quinoxalinyl,

[0103] phthalazinyl,

[0104] imidazolyl,

[0105] isoxazolyl,

[0106] pyrazolyl,

[0107] oxazolyl,

[0108] thiazolyl,

[0109] indolizinyl,

[0110] indazolyl,

[0111] benzothiazolyl,

[0112] benzimidazolyl,

[0113] benzofuiranyl,

[0114] faranyl,

[0115] thienyl,

[0116] pyrrolyl,

[0117] oxadiazolyl,

[0118] thiadiazolyl,

[0119] triazolyl,

[0120] tetrazolyl,

[0121] oxazolopyridinyl,

[0122] imidazopyridinyl,

[0123] isothiazolyl,

[0124] naphthyridinyl,

[0125] cinnolinyl,

[0126] carbazolyl,

[0127] beta-carbolinyl,

[0128] isochromanyl,

[0129] chromanyl,

[0130] tetrahydroisoquinolinyl,

[0131] isoindolinyl,

[0132] isobenzotetrahydrofuranyl,

[0133] isobenzotetrahydrothienyl,

[0134] isobenzothienyl,

[0135] benzoxazolyl,

[0136] pyridopyridinyl,

[0137] benzotetrahydrofuranyl,

[0138] benzotetrahydrothienyl,

[0139] purinyl,

[0140] benzodioxolyl,

[0141] triazinyl,

[0142] phenoxazinyl,

[0143] phenothiazinyl,

[0144] pteridinyl,

[0145] benzothiazolyl,

[0146] imidazopyridinyl,

[0147] imidazothiazolyl,

[0148] dihydrobenzisoxazinyl,

[0149] benzisoxazinyl,

[0150] benzoxazinyl,

[0151] dihydrobenzisothiazinyl,

[0152] benzopyranyl,

[0153] benzothiopyranyl,

[0154] coumarinyl,

[0155] isocoumarinyl,

[0156] chromonyl,

[0157] chromanonyl,

[0158] pyridinyl-N-oxide

[0159] tetrahydroquinolinyl

[0160] dihydroquinolinyl

[0161] dihydroquinolinonyl

[0162] dihydroisoquinolinonyl

[0163] dihydrocoumarinyl

[0164] dihydroisocoumarinyl

[0165] isoindolinonyl

[0166] benzodioxanyl

[0167] benzoxazolinonyl

[0168] pyrrolyl N-oxide,

[0169] pyrimidinyl N-oxide,

[0170] pyridazinyl N-oxide,

[0171] pyrazinyl N-oxide,

[0172] quinolinyl N-oxide,

[0173] indolyl N-oxide,

[0174] indolinyl N-oxide,

[0175] isoquinolyl N-oxide,

[0176] quinazolinyl N-oxide,

[0177] quinoxalinyl N-oxide,

[0178] phthalazinyl N-oxide,

[0179] imidazolyl N-oxide,

[0180] isoxazolyl N-oxide,

[0181] oxazolyl N-oxide,

[0182] thiazolyl N-oxide,

[0183] indolizinyl N-oxide, t

[0184] indazolyl N-oxide,

[0185] benzothiazolyl N-oxide,

[0186] benzimidazolyl N-oxide,

[0187] pyrrolyl N-oxide,

[0188] oxadiazolyl N-oxide,

[0189] thiadiazolyl N-oxide,

[0190] triazolyl N-oxide,

[0191] tetrazolyl N-oxide,

[0192] benzothiopyranyl S-oxide,

[0193] benzothiopyranyl S,S-dioxide,

[0194] where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by anyring atom of the parent R_(N-heteroaryl) group substituted by hydrogensuch that the new bond to the R_(1-heteroaryl) group replaces thehydrogen atom and its bond, where heteroaryl is optionally substitutedwith one, two, three or four of:

[0195] (1) C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above, —C≡N, —CF₃, C₁-C₃ alkoxy,

[0196] (2) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0197] (3) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b are —H or C) ₁-C₆ alkyl,

[0198] (4) —F, —Cl, —Br and —I,

[0199] (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three—F,

[0200] (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedbelow,

[0201] (8) —OH,

[0202] (9) —C≡N,

[0203] (10) C₃-C₇ cycloalkyl, optionally substituted with one, two orthree substituents selected from the group consisting of —F, —Cl, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl,

[0204] (11) —CO—(C₁-C₄ alkyl),

[0205] (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0206] (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0207] (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zeroR_(1-heteroaryl) is not bonded to the carbon chain by nitrogen,

[0208] (VIII) —(CH₂)_(n-1)(R_(1-heterocycle)) where n₁ is as definedabove and R_(1-heterocycle) is selected from the group consisting of:

[0209] morpholinyl,

[0210] thiomorpholinyl,

[0211] thiomorpholinyl S-oxide,

[0212] thiomorpholinyl S,S-dioxide,

[0213] piperazinyl,

[0214] homopiperazinyl,

[0215] pyrrolidinyl,

[0216] pyrrolinyl,

[0217] tetrahydropyranyl,

[0218] piperidinyl,

[0219] tetrahydrofuranyl,

[0220] tetrahydrothienyl,

[0221] homopiperidinyl,

[0222] homomorpholinyl,

[0223] homothiomorpholinyl,

[0224] homothiomorpholinyl S,S-dioxide, and

[0225] oxazolidinonyl,

[0226] dihydropyrazolyl

[0227] dihydropyrrolyl

[0228] dihydropyrazinyl

[0229] dihydropyridinyl

[0230] dihydropyrimidinyl

[0231] dihydrofuryl

[0232] dihydropyranyl

[0233] tetrahydrothienyl S-oxide

[0234] tetrahydrothienyl S,S-dioxide

[0235] homothiomorpholinyl S-oxide

[0236] where the R_(1-heterocycle) group is bonded by any atom of theparent R_(1-heterocycle) group substituted by hydrogen such that the newbond to the R_(1-heterocycle) group replaces the hydrogen atom and itsbond, where heterocycle is optionally substituted with one, two, threeor four:

[0237] (1) C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above, —C≡N, —CF₃, C₁-C₃ alkoxy,

[0238] (2) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0239] (3) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0240] (4) —F, —Cl, —Br and —I,

[0241] (5) C₁-C₆ alkoxy,

[0242] (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three—F,

[0243] (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedbelow,

[0244] (8) —OH,

[0245] (9) —C—N,

[0246] (10) C₃-C₇ cycloalkyl, optionally substituted with one, two orthree substituents selected from the group consisting of —F, —Cl, —OH,—SH —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b)are —H or C₁-C₆ alkyl,

[0247] (11) —CO—(C₁-C₄ alkyl),

[0248] (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0249] (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0250] (14) —SO₂—(C₁-C₄ alkyl),

[0251] (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle)is not bonded to the carbon chain by nitrogen;

[0252] where R₂ is selected from the group consisting of:

[0253] (II) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0254] (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl)where R_(1-aryl) and R_(1-heteroaryl) are as defined above;

[0255] (IV) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0256] (V) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0257] (VI) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of —F, —Cl,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl, where R₃ is selected from the groupconsisting of:

[0258] (I) —H,

[0259] (II) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0260] (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl)where R_(1-aryl) and R_(1-heteroaryl) are as defined above;

[0261] (IV) C₂-C₆ alkenyl with one or two double bonds,

[0262] (V) C₂-C₆ alkynyl with one or two triple bonds,

[0263] (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of —F, —Cl,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken togetherwith the carbon to which they are attached to form a carbocycle ofthree, four, five, six, and seven carbon atoms, optionally where onecarbon atom is replaced by a heteroatom selected from the groupconsisting of —O—, —S—, —SO₂—, —NR_(N-2)—, where R_(N-2) is as definedbelow;

[0264] where R_(N) is:

[0265] (I) R_(N-1)—X_(N)— where X_(N) is selected from the groupconsisting of:

[0266] (A) —CO—,

[0267] (B) —SO₂—

[0268] (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are—H and C₁-C₄ alkyl,

[0269] (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from thegroup consisting of —O—, —S— and —NR′— and where R′ and R″ are asdefined above,

[0270] (E) a single bond;

[0271] where R_(N-1) is selected from the group consisting of:

[0272] (A) R_(N-aryl) where R_(N-aryl) is phenyl, 1-naphthyl,2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted withone, two or three of the following substituents which can be the same ordifferent and are:

[0273] (1) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0274] (2) —OH,

[0275] (3) —NO₂,

[0276] (4) —F, —Cl, —Br, —I,

[0277] (5) —CO—OH,

[0278] (6) —C≡N,

[0279] (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are selected from the group consisting of:

[0280] (a) —H,

[0281] (b) —C₁-C₆ alkyl optionally substituted with one substitutentselected from the group consisting of:

[0282] (i) —OH,

[0283] (ii) —NH₂,

[0284] (c) —C₁-C₆ alkyl optionally substituted with one to three —F,—Cl, —Br, —I,

[0285] (d) —C₃-C₇ cycloalkyl,

[0286] (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl),

[0287] (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl),

[0288] (g) —C₂-C₆ alkenyl with one or two double bonds,

[0289] (h) —C₂-C₆ alkynyl with one or two triple bonds,

[0290] (i) —C₁-C₆ alkyl chain with one double bond and one triple bond,

[0291] (j) —R_(1-aryl) where R_(1-aryl) is as defined above,

[0292] (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above,

[0293] (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),

[0294] (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three doublebonds),

[0295] (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triplebonds),

[0296] (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl),

[0297] (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as definedabove,

[0298] (13) —CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is asdefined above,

[0299] (14) —CH₂)₀₋₄—CO—R_(1-heterocycle) where R1 _(1-heterocycle) isas defined above,

[0300] (15) —CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the groupconsisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl,homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide,homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where eachgroup is optionally substituted with one, two, three, or four of C₁-C₆alkyl,

[0301] (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from thegroup consisting of:

[0302] (a) C₁-C₆ alkyl,

[0303] (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above,

[0304] (c) C₂-C₆ alkenyl containing one or two double bonds,

[0305] (d) C₂-C₆ alkynyl containing one or two triple bonds,

[0306] (e) C₃-C₇ cycloalkyl,

[0307] (f) —CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is asdefined above,

[0308] (17) —CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) areas defined above,

[0309] (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl),

[0310] (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl),

[0311] (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl),

[0312] (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can bethe same or different and is as defined above,

[0313] (22) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—N(R_(N-5))₂, where R_(N-5) canbe the same or different and is as defined above,

[0314] (23) —(CH₂)₀₋₄-N—CS—N(R_(N-5))₂, where R_(N-5) can be the same ordifferent and is as defined above,

[0315] (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as defined above,

[0316] (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can bethe same or different and are as defined above,

[0317] (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above,

[0318] (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),

[0319] (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —Hor C₁-C₄ alkyl,

[0320] (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[0321] (30) —(CH₂)₀₋₄—CS—N(R_(N-5))₂ where R_(N-5) is as defined above,

[0322] (31) —CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above,

[0323] (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as definedabove,

[0324] (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above,

[0325] (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one,two, three, four, or five of —F),

[0326] (35) C₃-C₇ cycloalkyl,

[0327] (36) C₂-C₆ alkenyl with one or two double bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0328] (37) C₂-C₆ alkynyl with one or two triple bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0329] (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as described above,

[0330] (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl,

[0331] (B) —R_(N-heteroaryl) where R_(N-heteroaryl) is selected from thegroup consisting of:

[0332] pyridinyl,

[0333] pyrimidinyl,

[0334] quinolinyl,

[0335] benzothienyl,

[0336] indolyl,

[0337] indolinyl,

[0338] pryidazinyl,

[0339] pyrazinyl,

[0340] isoindolyl,

[0341] isoquinolyl,

[0342] quinazolinyl,

[0343] quinoxalinyl,

[0344] phthalazinyl,

[0345] imidazolyl,

[0346] isoxazolyl,

[0347] pyrazolyl,

[0348] oxazolyl,

[0349] thiazolyl,

[0350] indolizinyl,

[0351] indazolyl,

[0352] benzothiazolyl,

[0353] benzimidazolyl,

[0354] benzofuranyl,

[0355] furanyl,

[0356] thienyl,

[0357] pyrrolyl,

[0358] oxadiazolyl,

[0359] thiadiazolyl,

[0360] triazolyl,

[0361] tetrazolyl,

[0362] oxazolopyridinyl,

[0363] imidazopyridinyl,

[0364] isothiazolyl,

[0365] naphthyridinyl,

[0366] cinnolinyl,

[0367] carbazolyl,

[0368] beta-carbolinyl,

[0369] isochromanyl,

[0370] chromanyl,

[0371] tetrahydroisoquinolinyl,

[0372] isoindolinyl,

[0373] isobenzotetrahydrofuranyl,

[0374] isobenzotetrahydrothienyl,

[0375] isobenzothienyl,

[0376] benzoxazolyl,

[0377] pyridopyridinyl,

[0378] benzotetrahydrofuranyl,

[0379] benzotetrahydrothienyl,

[0380] purinyl,

[0381] benzodioxolyl,

[0382] triazinyl,

[0383] henoxazinyl,

[0384] phenothiazinyl,

[0385] pteridinyl,

[0386] benzothiazolyl,

[0387] imidazopyridinyl,

[0388] imidazothiazolyl,

[0389] dihydrobenzisoxazinyl,

[0390] benzisoxazinyl,

[0391] benzoxazinyl,

[0392] dihydrobenzisothiazinyl,

[0393] benzopyranyl,

[0394] benzothiopyranyl,

[0395] coumarinyl,

[0396] isocoumarinyl,

[0397] chromonyl,

[0398] chromanonyl,

[0399] pyridinyl-N-oxide,

[0400] tetrahydroquinolinyl

[0401] dihydroquinolinyl

[0402] dihydroquinolinonyl

[0403] dihydroisoquinolinonyl

[0404] dihydrocoumarinyl

[0405] dihydroisocoumarinyl

[0406] isoindolinonyl

[0407] benzodioxanyl

[0408] benzoxazolinonyl

[0409] pyrrolyl N-oxide,

[0410] pyrimidinyl N-oxide,

[0411] pyridazinyl N-oxide,

[0412] pyrazinyl N-oxide,

[0413] quinolinyl N-oxide,

[0414] indolyl N-oxide,

[0415] indolinyl N-oxide,

[0416] isoquinolyl N-oxide,

[0417] quinazolinyl N-oxide,

[0418] quinoxalinyl N-oxide,

[0419] phthalazinyl N-oxide,

[0420] imidazolyl N-oxide,

[0421] isoxazolyl N-oxide,

[0422] oxazolyl N-oxide,

[0423] thiazolyl N-oxide,

[0424] indolizinyl N-oxide,

[0425] indazolyl N-oxide,

[0426] benzothiazolyl N-oxide,

[0427] benzimidazolyl N-oxide,

[0428] pyrrolyl N-oxide,

[0429] oxadiazolyl N-oxide,

[0430] thiadiazolyl N-oxide,

[0431] triazolyl N-oxide,

[0432] tetrazolyl N-oxide,

[0433] benzothiopyranyl S-oxide ,

[0434] benzothiopyranyl N ,S-dioxide,

[0435] where the R_(N-heteroaryl) group is bonded by any atom of theparent R_(N-heteroaryl) group substituted by hydrogen such that the newbond to the R_(N-heteroaryl) group replaces the hydrogen atom and itsbond, where heteroaryl is optionally substituted with one, two, three,or four of:

[0436] (1) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting Of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, CL-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0437] (2) —OH,

[0438] (3) —NO₂,

[0439] (4) —F, —Cl, —Br, —I,

[0440] (5) —CO—OH,

[0441] (6) —C≡N,

[0442] (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are selected from the group consisting of:

[0443] (a) —H,

[0444] (b) —C₁-C₆ alkyl optionally substituted with one substitutentselected from the group consisting of:

[0445] (i) —OH,

[0446] (ii) —NH₂,

[0447] (c) —C₁-C₆ alkyl optionally substituted with one to three —F,—Cl, —Br, —I,

[0448] (d) —C₃-C₇ cycloalkyl,

[0449] (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl),

[0450] (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl),

[0451] (g) —C₂-C₆ alkenyl with one or two double bonds,

[0452] (h) —C₂-C₆ alkynyl with one or two triple bonds,

[0453] (i) —C₁-C₆ alkyl chain with one double bond and one triple bond,

[0454] (j) —R_(1-aryl) where R_(1-aryl) is as defined above,

[0455] (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above,

[0456] (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),

[0457] (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three doublebonds),

[0458] (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triplebonds),

[0459] (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl),

[0460] (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as definedabove,

[0461] (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is asdefined above,

[0462] (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above,

[0463] (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from thegroup consisting of morpholinyl, thiomorpholinyl, piperazinyl,piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinylS-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinylwhere each group is optionally substituted with one, two, three, or fourof C₁-C₆ alkyl,

[0464] (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from thegroup consisting of:

[0465] (a) C₁-C₆ alkyl,

[0466] (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above,

[0467] (c) C₂-C₆ alkenyl containing one or two double bonds,

[0468] (d) C₂-C₆ alkynyl containing one or two triple bonds,

[0469] (e) C₃-C₇ cycloalkyl,

[0470] (f) —CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is asdefined above,

[0471] (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) areas defined above,

[0472] (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl),

[0473] (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl),

[0474] (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl),

[0475] (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can bethe same or different and is as defined above,

[0476] (22) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—N(R_(N-5))₂, where R_(N-5) canbe the same or different and is as defined above,

[0477] (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same ordifferent and is as defined above,

[0478] (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as defined above,

[0479] (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can bethe same or different and are as defined above,

[0480] (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above,

[0481] (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),

[0482] (28) —(CH₂)₀₋₄—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H orC₁-C₄ alkyl,

[0483] (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[0484] (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[0485] (31) —CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above,

[0486] (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as definedabove,

[0487] (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above,

[0488] (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one,two, three, four, or five of —F),

[0489] (35) C₃-C₇ cycloalkyl,

[0490] (36) C₂-C₆ alkenyl with one or two double bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0491] (37) C₂-C₆ alkynyl with one or two triple bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0492] (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as described above,

[0493] (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl,

[0494] (C) R_(N-aryl)—W—R_(N-aryl),

[0495] (D) R_(N-aryl)—W—R_(N-heteroaryl),

[0496] (E) R_(N-aryl)—W—R_(N-1-heterocycle), where R_(N-heterocycle) isdefined as R_(1-heterocycle) is defined above,

[0497] (F) R_(N-heteroaryl)—W—R_(N-aryl),

[0498] (G) R_(N-heteroaryl)—W—R_(N-heteroaryl),

[0499] (H) R_(N-heteroaryl)—W—R_(N-1-heterocycle), whereR_(N-1-heterocycle) is defined as R_(1-heterocycle) is defined above,

[0500] (I) R_(N-heterocycle)—W—R_(N-aryl),

[0501] (J) R_(N-heterocycle)—W—R_(N-heteroaryl),

[0502] (K) R_(N-heterocycle)—W—R_(N-1-heterocycle),

[0503] where W is

[0504] (1) —(CH₂)₀₋₄—,

[0505] (2) —O—,

[0506] (3) —S(O)₀₋₂—,

[0507] (4) —N(R_(N-5))— where R_(N-5) is as defined above, or

[0508] (5) —CO—;

[0509] (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substitutedwith one two or three substitutents selected from the group consistingof:

[0510] (A) —OH,

[0511] (B) —C₁-C₆ alkoxy,

[0512] (C) —C₁-C₆ thioalkoxy,

[0513] (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl,

[0514] (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[0515] (F) —CO—RN₄ where R_(N-4) is as defined above,

[0516] (G) —SO₂—(C₁-C₈ alkyl),

[0517] (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the sameor different and are as defined above,

[0518] (I) —NH—CO—(C₁-C₆ alkyl),

[0519] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[0520] (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[0521] (L) —R_(N-4) where R_(N-4) is as defined above,

[0522] (M) —O—CO—(C₁-C₆ alkyl),

[0523] (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or differentand are as defined above,

[0524] (O) —O—(C₁-C₅ alkyl)—COOH,

[0525] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof —F, —CI, —Br, —I),

[0526] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[0527] (R) —F, —Cl,

[0528] (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl is optionallysubstituted with one, two, or three substitutents selected from thegroup consisting of:

[0529] (A) —OH,

[0530] (B) —C₁-C₆ alkoxy,

[0531] (C) —C₁-C₆ thioalkoxy,

[0532] (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl,

[0533] (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[0534] (F) —CO—R_(N-4) where R_(N-4) is as defined above,

[0535] (G) —SO₂—(C₁-C8 alkyl),

[0536] (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the sameor different and are as defined above,

[0537] (I) —NH—CO—(C₁-C₆ alkyl),

[0538] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[0539] (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[0540] (L) —R_(N-4) where R_(N-4) is as defined above,

[0541] (M) —O—CO—(C₁-C₆ alkyl),

[0542] (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or differentand are as defined above,

[0543] (O) —O—(C₁-C₅ alkyl)—COOH,

[0544] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof —F, —CI, —Br, —I),

[0545] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[0546] (R) —F, —Cl,

[0547] (IV) —CO—(C₁-C₆ alkyl)—S—(C₁-C₆ alkyl) where alkyl is optionallysubstituted with one, two, or three of substitutents selected from thegroup consisting of:

[0548] (A) —OH,

[0549] (B) —C₁-C₆ alkoxy,

[0550] (C) —C₁-C₆ thioalkoxy,

[0551] (D) —CO—O—R_(N-8) where R_(N-8) is as defined above,

[0552] (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[0553] (F) —CO—R_(N-4) where R_(N-4) is as defined above,

[0554] (G) —SO₂—(C₁-C₈ alkyl),

[0555] (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the sameor different and are as defined above,

[0556] (I) —NH—CO—(C₁-C₆ alkyl),

[0557] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[0558] (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[0559] (L) —R_(N-4) where R_(N-4) is as defined above,

[0560] (M) —O—CO—(C₁-C₆ alkyl),

[0561] (N) —O—CO—NR_(N-8)R_(N-8) where the RN8s are the same ordifferent and are as defined above,

[0562] (O) —O—(C₁-C₅ alkyl)—COOH,

[0563] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof —F, —Cl, —Br, —I),

[0564] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[0565] (R) —F, —C,

[0566] (V)—CO—CH(—(CH₂)₀₋₂—O—R_(N-10))—(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)) whereR_(N-aryl) and R_(N-heteroaryl) are as defined above, where R_(N-10) isselected from the group consisting of:

[0567] (A) —H,

[0568] (B) C₁-C₆ alkyl,

[0569] (C) C₃-C₇ cycloalkyl,

[0570] (D) C₂-C₆ alkenyl with one double bond,

[0571] (E) C₂-C₆ alkynyl with one triple bond,

[0572] (F) R_(1-aryl) where R_(1-aryl) is as defined above,

[0573] (G) R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above,

[0574] (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substitutedwith one or two substitutents selected from the group consisting of:

[0575] (A) —(CH₂)₀₋₄—OH,

[0576] (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy,

[0577] (C) —(CH₂)₀₋₄-C₁-C₆ thioalkoxy,

[0578] (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or-phenyl,

[0579] (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are as defined above,

[0580] (F) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is as defined above,

[0581] (G) —(CH₂)₀₋₄—SO₂—(C₁-C₈ alkyl),

[0582] (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are as defined above,

[0583] (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl),

[0584] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[0585] (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are thesame or different and are as defined above,

[0586] (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above,

[0587] (M) —O—CO—(C₁-C₆ alkyl),

[0588] (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same ordifferent and are as defined above,

[0589] (O) —O—(C₁-C₅ alkyl)—COOH,

[0590] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof —F, —Cl, —Br, —I),

[0591] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[0592] (R) —F, —Cl,

[0593] where R_(C) is:

[0594] (I) —C₁-C₁₀ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) whereR_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a)and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a)and R_(1-b) are as defined above,

[0595] (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can beoptionally substituted with one, two or three substituents selected fromthe group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N,—CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO-O—(C₁-C₄ alkyl),—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0596] (III) —(CR_(C-x)R_(C-y))₀₋₄R_(C-aryl) where R_(C-x) and R_(C-y)are

[0597] —H,

[0598] C₁-C₄ alkyl optionally substituted with one or two —OH,

[0599] C₁-C₄ alkoxy optionally substituted with one, two, or three of—F,

[0600] —(CH₂)₀₋₄-C₃-C₇ cycloalkyl,

[0601] C₂-C₆ alkenyl containing one or two double bonds,

[0602] C₂-C₆ alkynyl containing one or two triple bonds, phenyl,

[0603] and where R_(C-x) and R_(C-y) are taken together with the carbonto which they are attached to form a carbocycle of three, four, five,six and seven carbon atoms, optionally where one carbon atom is replacedby a heteroatom selected from the group consisting of —O—, —S—, —SO₂—,—NR_(N-2)— and R_(C-aryl) is defined as R_(N-aryl) is defined above;

[0604] (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) whereR_(C-heteroaryl) is defined as R_(N-heteroaryl) is defined above andR_(C-x) and R_(C-y) are as defined above,

[0605] (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-aryl),R_(C-x) and R_(C-y) are as defined above,

[0606] (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) whereR_(C-aryl), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above,

[0607] (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) whereR_(C-heteroaryl), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above,

[0608] (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl)where R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above,

[0609] (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) whereR_(C-aryl), R_(C-x) and R_(C-y) are as defined above, andR_(C-heterocycle) is defined as R_(N-heterocycle) is defined above,

[0610] (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle)where R_(C-heteroaryl), R_(C-heterocycle), R_(C-x) and R_(C-y) are asdefined above,

[0611] (XI) —(CR_(C-x)R_(C-y))₀₋₄R_(C-heterocycle)—R_(C-aryl) whereR_(C-heterocycle), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above,

[0612] (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl)where R_(C-heterocycle), R_(C-heteroaryl), R_(C-x) and R_(C-y) are asdefined above,

[0613] (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle)where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above,

[0614] (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) whereR_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above,

[0615] (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) andR_(C-2) are the same or different and are selected from the groupconsisting of:

[0616] (A) —H,

[0617] (B) —C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above,

[0618] (C) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0619] (D) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0620] (E) —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl),

[0621] (F) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of C₁-C₃alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0622] (G) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as definedfor R_(1-aryl),

[0623] (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is asdefined above,

[0624] (I) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) isas defined above,

[0625] (J) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above,

[0626] (K) —R_(C-heterocycle) where R_(C-heterocycle) is as definedabove,

[0627] (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—,-S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, and where R_(C′-aryl) isdefined above,

[0628] (N) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) andR_(C-heteroaryl) are as defined above,

[0629] (O) —R_(C′-aryl) where R_(C′-aryl) is as defined above,

[0630] and where R_(C-3) is the same or different and is:

[0631] (A) —H,

[0632] (B) —C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b)where R_(1-a) and R1-b are as defined above,

[0633] (C) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0634] (D) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0635] (E) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of C₁-C₃alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0636] (F) —R_(C′-aryl) where R_(C′-aryl) is as defined above,

[0637] (G) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above,

[0638] (H) —R_(C-heterocycle) where R_(C-heterocycle) is as definedabove,

[0639] (I) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as definedabove,

[0640] (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is asdefined above,

[0641] (K) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) isas defined above,

[0642] (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or differentand are as defined above,

[0643] (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the sameor different and are as defined above,

[0644] (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)) where R_(C-aryl) andR_(C-heteroaryl) are as defined above,

[0645] (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused toR_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) orR_(C-heteroaryl) or R_(C-heterocycle) are as defined above where onecarbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionallyreplaced with NH, NR_(N-5), O, S(═O)₀₋₂, and where cyclopentyl,cyclohexyl, or -cycloheptyl can be optionally substituted with one ortwo —C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, ═O,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0646] (XX) C₂-C₁₀ alkenyl containing one or two double bonds optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0647] (XXI) C₂-C₁₀ alkynyl containing one or two trple bonds optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0648] (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-aryl) where R_(C-aryl) isas defined above and R_(C-6) is —(CH₂)₀₋₆—OH,

[0649] (XXII) —(CH₂)₀₋₁—CHR_(C-6)—CH₂)₀₋₁—R_(C-heteroaryl) whereR_(C-heteroaryl) and R_(C-6) is as defined above,

[0650] (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl))—CO—O(C₁-C₄ alkyl)where R_(C-aryl) and R_(C-heteroaryl) are as defined above,

[0651] (XXIV) —CH(—CH₂—OH)—CH(—OH)-micro-NO₂,

[0652] (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH,

[0653] (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂,

[0654] (XXVIII) —H,

[0655] (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) andR_(1-b) are as defined above, and pharmaceutically acceptable saltsthereof.

[0656] Also disclosed is a substituted amine of the formula (X′)

[0657] where R₁, R₂, R₃ and R_(C) are as defined above;

[0658] where Ring A is phenyl, 1-naphthyl and 2-naphthyl optionallysubstituted with one, two or three of the following substituents whichcan be the same or different and are:

[0659] (1) C₁-C₆ alkyl,

[0660] (2) —F, —Cl, —Br, I,

[0661] (3) —OH,

[0662] (4) —NO₂,

[0663] (5) —CO—OH,

[0664] (6) —C≡N,

[0665] (7) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedabove,

[0666] (8) —CO—(C₃-C₁₂ alkyl),

[0667] (9) —CO—(C₃-C₆ cycloalkyl),

[0668] (10) —CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined inabove,

[0669] (11) —CO—R_(1-heterocycle) where R_(1-heterocycle) is as definedin above,

[0670] (12) —CO—R_(N-4) where R_(N-4) is as defined in above,

[0671] (13) —CO—O—R_(N-5) where R_(N-5) is as defined in above,

[0672] (14) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are asdefined above,

[0673] (15) —SO—(C₁-C₈ alkyl),

[0674] (16) —SO₂—(C₃-C₁₂ alkyl) with the proviso that the alkyl groupnot be straight chained,

[0675] (17) —NH—CO—O—R_(N-5) where R_(N-5) is as defined above,

[0676] (18) —NH—CO—N(C₁-C₃ alkyl)₂,

[0677] (19) —N—CS—N(C₁-C₃ alkyl)₂,

[0678] (20) —N(—H or C₁-C₃ alkyl)—CO—R_(N-5) where R_(N-5) is as definedabove,

[0679] (21) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the sameor different and are as defined above,

[0680] (22) —R_(N-4) where R_(N-4) is as defined above,

[0681] (23) —O—CO—(C₁-C₆ alkyl),

[0682] (24) —O—CO—N(C₁-C₃ alkyl)₂,

[0683] (25) —O—CS—N(C₁-C₃ alkyl)₂,

[0684] (26) —O—(C₁-C₆ alkyl),

[0685] (27) —O—(C₂-C₅ alkyl)—COOH,

[0686] (28) —S—(C₁-C₆ alkyl) and pharmaceutically acceptable saltsthereof.

[0687] Additionally disclosed is a protected compound of the formula(III)

[0688] where R₁, R₂ and R₃ are as defined above;

[0689] where X₁ is —Cl, —Br, —I, —O-tosylate, —O-mesylate, —O-nosylate;

[0690] where PROTECTING GROUP is selected from the group consisting oft-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl,trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl,difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl,2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl,4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl,3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl,2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl,3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl,4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl,1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl,2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl,cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl,cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl,2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl,2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl,fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl,allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl,5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl,2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl,cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl,isobomyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethylcarbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.

[0691] Further disclosed is an alcohol of the formula (IV)

[0692] where R₁, R₂, R₃, X₁ and PROTECTING GROUP are as defined above.

[0693] Additionally disclosed is an epoxide of the formula (V)

[0694] where R₂, R₃ and PROTECTING GROUP are as defined above and whereR₁ is:

[0695] —CH₂-phenyl where -phenyl is substituted with two —F,

[0696] —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-heteroaryl) is as definedabove, and

[0697] —(CH₂)_(n1)—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above.

[0698] Further disclosed is a protected alcohol of the formula (VII)

[0699] where R₂, R₃, R_(C) and PROTECTING GROUP are as defined above,and where R₁ is:

[0700] —(CH₂-phenyl where -phenyl is substituted with two —F,

[0701] —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-heteroaryl) is as definedabove and

[0702] —(CH₂)_(n1)—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above and chemically acceptable salts thereof.

[0703] Also disclosed is an amine of the formula (VIII)

[0704] where R₂, R₃ and R_(C) are as defined above and where R₁ is:

[0705] —(CH₂-phenyl where -phenyl is substituted with two —F,

[0706] —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-heteroaryl) is as definedabove and

[0707] —(CH₂)_(n1)—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above and chemically acceptable salts thereof.

[0708] Disclosed is a protected ketone of formula (XI)

[0709] where R₂, R₃, R_(C) and PROTECTING GROUP are as defined above andwhere R₁ is:

[0710] —CH₂-phenyl where -phenyl is substituted with two —F,

[0711] —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-heteroaryl) is as definedabove and

[0712] —(CH₂)_(n1)—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above.

[0713] Also disclosed is a protected azide of formula (XII)

[0714] where R₂, R₃ and PROTECTING GROUP are as defined above and whereR₁ is:

[0715] —CH₂-phenyl where -phenyl is substituted with two —F,

[0716] —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-hetroaryl) is as definedabove and

[0717] —(CH₂)_(n1)—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above.

[0718] Further disclosed is a protected amine of formula (XIII)

[0719] where R₂, R₃ and PROTECTING GROUP are as defined above and whereR₁ is:

[0720] —CH₂-phenyl where -phenyl is substituted with two —F,

[0721] —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-heteroaryl) is as definedabove and

[0722] —(CH₂)_(n1)—R_(1-heteroycle) where R_(1-heterocycle) is asdefined above.

[0723] Additionally disclosed is an unprotected azide of formula (XIV)

[0724] where R₁, R₂, R₃ and PROTECTING GROUP are as defined above forthe substituted amine (X).

[0725] Further disclosed is an azide of formula (XV)

[0726] where R₁, R₂, R₃ and R_(N) are as defined above for thesubstituted amine (X).

[0727] Also disclosed is a free amine of formula (XVI)

[0728] where R₂, R₃ and R_(N) are as defined above and where R₁ is:

[0729] (A) —CH₂-phenyl where -phenyl is substituted with two —F,

[0730] (B) —(CH₂)_(n1)—R_(1-heteroaryl) where R_(1-heteroaryl) is asdefined above and

[0731] (C) —(CH₂)_(n1)—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above.

[0732] Disclosed is a method of treating a patient who has, or inpreventing a patient from getting, a disease or condition selected fromthe group consisting of Alzheimer's disease, for helping prevent ordelay the onset of Alzheimer's disease, for treating patients with mildcognitive impairment (MCI) and preventing or delaying the onset ofAlzheimer's disease in those who would progress from MCI to AD, fortreating Down's syndrome, for treating humans who have HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treatingcerebral amyloid angiopathy and preventing its potential consequences,i.e. single and recurrent lobar hemorrhages, for treating otherdegenerative dementias, including dementias of mixed vascular anddegenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, or diffuse Lewy body typeof Alzheimer's disease and who is in need of such treatment whichcomprises administration of a therapeutically effective amount of acompound selected from the group consisting of a substituted amine offormula (X)

[0733] where R₁, R₂, R₃, R_(C), and R_(N) are as defined above for thesubstituted amine (X), and pharmaceutically acceptable salts thereof,and

[0734] a substituted amine with R_(N) cyclized of formula (X′)

[0735] where R₁, R₂, R₃, R_(C), and Ring A, are as defined above for theamine (X′), and pharmaceutically acceptable salts thereof.

[0736] Also disclosed are methods for inhibiting beta-secretaseactivity, for inhibiting cleavage of amyloid precursor protein (APP), ina reaction mixture, at a site between Met596 and Asp597, numbered forthe APP-695 amino acid isotype; or at a corresponding site of an isotypeor mutant thereof, for inhibiting production of amyloid beta peptide (Abeta) in a cell, for inhibiting the production of beta-amyloid plaque inan animal, and for treating or preventing a disease characterized bybeta-amyloid deposits in the brain which comprise administration of atherapeutically effective amount of a substituted amine of formula (X)

[0737] where R₁, R₂, R₃, R_(C), and R_(N) are as defined above for thesubstituted amine (X), and pharmaceutically acceptable salts thereof.

[0738] Disclosed is a pharmaceutial composition which comprises asubstituted amine of formula (X)

[0739] where R₁, R₂, R₃, R_(N) and R_(C) are as defined above for thesubstituted amine (X), or a substituted amine with R_(N) cyclized offormula (X′)

[0740] where R₁ is as defined above for compound (X′) and where Ring Ais as defined above, and pharmaceutically acceptable salts thereof, andone or more pharmaceutically acceptable inert carriers.

[0741] Disclosed is the use of a substituted amine of formula (X)

[0742] where R₁, R₂, R₃, R_(N) and R_(C) are as defined above for thesubstituted amine (X), or a substituted amine with R_(N) cyclized offormula (X′)

[0743] where R₁, R₂, R₃, R_(C), and Ring A, are as defined above forcompound (X′), and pharmaceutically acceptable salts thereof for themanufacture of a medicament for use in treating a patient who has, or inpreventing a patient from getting, a disease or condition selected fromthe group consisting of Alzheimer's disease, for helping prevent ordelay the onset of Alzheimer's disease, for treating patients with mildcognitive impairment (MCI) and preventing or delaying the onset ofAlzheimer's disease in those who would progress from MCI to AD, fortreating Down's syndrome, for treating humans who have HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treatingcerebral amyloid angiopathy and preventing its potential consequences,i.e. single and recurrent lobar hemorrhages, for treating otherdegenerative dementias, including dementias of mixed vascular anddegenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, diffuse Lewy body type ofAlzheimer's disease and who is in need of such treatment.

[0744] The present invention provides compounds, compositions, kits, andmethods for inhibiting beta-secretase-mediated cleavage of amyloidprecursor protein (APP). More particularly, the compounds, compositions,and methods of the invention are effective to inhibit the production ofA beta peptide and to treat or prevent any human or veterinary diseaseor condition associated with a pathological form of A beta peptide.

[0745] The compounds, compositions, and methods of the invention areuseful for treating humans who have Alzheimer's Disease (AD), forhelping prevent or delay the onset of AD, for treating patients withmild cognitive impairment (MCI), and preventing or delaying the onset ofAD in those patients who would otherwise be expected to progress fromMCI to AD, for treating Down's syndrome, for treating HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch Type, for treatingcerebral beta-amyloid angiopathy and preventing its potentialconsequences such as single and recurrent lobar hemorrhages, fortreating other degenerative dementias, including dementias of mixedvascular and degenerative origin, for treating dementia associated withParkinson's disease, dementia associated with progressive supranuclearpalsy, dementia associated with cortical basal degeneration, and diffuseLewy body type AD.

[0746] The compounds of the invention possess beta-secretase inhibitoryactivity. The inhibitory activities of the compounds of the inventionare readily demonstrated, for example, using one or more of the assaysdescribed herein or known in the art.

DETAILED DESCRIPTION OF THE INVENTION

[0747] The present invention is the substituted amines (X) that areuseful in treating and preventing Alzheimer's disease. Theanti-Alzheimer's substituted amines (X) are made by methods well knownto those skilled in the art from starting compounds known to thoseskilled in the art. The process chemistry is well known to those skilledin the art. The most general process to prepare the substituted amines(X) of the present invention is set forth in CHART A. The chemistry isstraight forward and in summary involves the steps of N-protecting anamino acid (I) starting material to produce the corresponding protectedamino acid (II), reaction of the protected amino acid (II) withdiazomethane followed by work-up to add a carbon atom to produce thecorresponding protected compound (III), reduction of the protectedcompound (III) to the corresponding alcohol (IV), formation of thecorresponding epoxide (V), opening of the epoxide (V) with a C-terminalamine, R_(C)—NH₂ (VI) to produce the corresponding protected alcohol(VII) which then has the nitrogen protecting group removed to producethe corresponding amine (VIII), which is then reacted with an amideforming agent of the formula (R_(N1)—X_(N))₂O or R_(N-1)—X_(N)—X₂ orR_(N-1)—X_(N)—OH (IX) to produce the anti-Alzheimer substituted amine(X). One skilled in the art will appreciate that these are all wellknown reactions in organic chemistry. A chemist skilled in the art,knowing the chemical structure of the biologically active substitutedamine end product (X) of the invention would be able to prepare them byknown methods from known starting materials without any additionalinformation. The explanation below therefore is not necessary but isdeemed helpful to those skilled in the art who desire to make thecompounds of the present invention.

[0748] The backbone of the compounds of the present invention is ahydroxyethylamine moiety, —NH—CH(R)—CH(OH)—. It can be readily preparedby methods disclosed in the literature and known to those skilled in theart. For example, J. Med. Chem., 36, 288-291 (1992), TetrahedronLetters, 28, 5569-5572 (1987), J. Med. Chem., 38, 581-584 (1994) andTetrahedron Letters, 38, 619-620 (1997) all disclose processes toprepare hydroxyethylamine type compounds.

[0749] CHART A sets forth a general method used in the present inventionto prepare the appropriately substituted amines (X). The anti-Alzheimersubstituted amines (X) of the present invention are prepared by startingwith the corresponding amino acid (I). The amino acids (I) are wellknown to those skilled in the art or can be readily prepared from knowncompounds by methods well known to those skilled in the art. Thesubstituted amines (X) of the present invention have at least twoenantiomeric centers which give four enantiomers. The first of theseenantiomeric centers derives from the amino acid starting material (I).It is preferred to commercially obtain or produce the desired enantiomer(S) rather than produce an enantiomerically impure mixture and then haveto separate out the desired enantiomer (S). It is preferred to start theprocess with enantiomerically pure (S)-amino acid (I) of the sameconfiguration as that of the substituted amine (X) product. For theamino acids (I), RI is:

[0750] (I) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F,—Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —OC═O NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0751] (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl),

[0752] (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl),

[0753] (IV) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0754] (V) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0755] (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and whereR_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl,dihydronaphthalyl, tetralinyl optionally substituted with one, two,three, or four of the following substituents on the aryl ring:

[0756] (A) C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above, —C≡N, —CF₃, C₁-C₃ alkoxy,

[0757] (B) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0758] (C) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0759] (D) —F, Cl, —Br and —I,

[0760] (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three—F,

[0761] (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedbelow,

[0762] (H) —OH,

[0763] (I) —C≡N,

[0764] (J) C₃-C₇ cycloalkyl, optionally substituted with one, two orthree substituents selected from the group consisting of —F, —Cl, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl,

[0765] (K) —CO—(C₁-C₄ alkyl),

[0766] (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0767] (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0768] (N) —SO₂—(C₁-C₄ alkyl),

[0769] (VII) —(CH₂)_(n1)—(R_(1-heterlaryl)) where n₁ is as defined aboveand where R_(1-heteroaryl) is selected from the group consisting of:

[0770] pyridinyl,

[0771] pyrimidinyl,

[0772] quinolinyl,

[0773] benzothienyl,

[0774] indolyl,

[0775] indolinyl,

[0776] pryidazinyl,

[0777] pyrazinyl,

[0778] isoindolyl,

[0779] isoquinolyl,

[0780] quinazolinyl,

[0781] quinoxalinyl,

[0782] phthalazinyl,

[0783] imidazolyl,

[0784] isoxazolyl,

[0785] pyrazolyl,

[0786] oxazolyl,

[0787] thiazolyl,

[0788] indolizinyl,

[0789] indazolyl,

[0790] benzothiazolyl,

[0791] benzimidazolyl,

[0792] benzofuranyl,

[0793] furanyl,

[0794] thienyl,

[0795] pyrrolyl,

[0796] oxadiazolyl,

[0797] thiadiazolyl,

[0798] triazolyl,

[0799] tetrazolyl,

[0800] oxazolopyridinyl,

[0801] imidazopyridinyl,

[0802] isothiazolyl,

[0803] naphthyridinyl,

[0804] cinnolinyl,

[0805] carbazolyl,

[0806] beta-carbolinyl,

[0807] isochromanyl,

[0808] chromanyl,

[0809] tetrahydroisoquinolinyl,

[0810] isoindolinyl,

[0811] isobenzotetrahydrofuranyl,

[0812] isobenzotetrahydrothienyl,

[0813] isobenzothienyl,

[0814] benzoxazolyl,

[0815] pyridopyridinyl,

[0816] benzotetrahydrofuranyl,

[0817] benzotetrahydrothienyl,

[0818] purinyl,

[0819] benzodioxolyl,

[0820] triazinyl,

[0821] phenoxazinyl,

[0822] phenothiazinyl,

[0823] pteridinyl,

[0824] benzothiazolyl,

[0825] imidazopyridinyl,

[0826] imidazothiazolyl,

[0827] dihydrobenzisoxazinyl,

[0828] benzisoxazinyl,

[0829] benzoxazinyl,

[0830] dihydrobenzisothiazinyl,

[0831] benzopyranyl,

[0832] benzothiopyranyl,

[0833] coumarinyl,

[0834] isocoumarinyl,

[0835] chromonyl,

[0836] chromanonyl,

[0837] pyridinyl-N-oxide

[0838] tetrahydroquinolinyl

[0839] dihydroquinolinyl

[0840] dihydroquinolinonyl

[0841] dihydroisoquinolinonyl

[0842] dihydrocoumarinyl

[0843] dihydroisocoumarinyl

[0844] isoindolinonyl

[0845] benzodioxanyl

[0846] benzoxazolinonyl

[0847] pyrrolyl N-oxide,

[0848] pyrimidinyl N-oxide,

[0849] pyridazinyl N-oxide,

[0850] pyrazinyl N-oxide,

[0851] quinolinyl N-oxide,

[0852] indolyl N-oxide,

[0853] indolinyl N-oxide,

[0854] isoquinolyl N-oxide,

[0855] quinazolinyl N-oxide,

[0856] quinoxalinyl N-oxide,

[0857] phthalazinyl N-oxide,

[0858] imidazolyl N-oxide,

[0859] isoxazolyl N-oxide,

[0860] oxazolyl N-oxide,

[0861] thiazolyl N-oxide,

[0862] indolizinyl N-oxide,

[0863] indazolyl N-oxide,

[0864] benzothiazolyl N-oxide,

[0865] benzimidazolyl N-oxide,

[0866] pyrrolyl N-oxide,

[0867] oxadiazolyl N-oxide,

[0868] thiadiazolyl N-oxide,

[0869] triazolyl N-oxide,

[0870] tetrazolyl N-oxide,

[0871] benzothiopyranyl S-oxide,

[0872] benzothiopyranyl S,S-dioxide,

[0873] where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by anyring atom of the parent R_(N-heteroaryl) group substituted by hydrogensuch that the new bond to the R_(1-heteroaryl) group replaces thehydrogen atom and its bond, where heteroaryl is optionally substitutedwith one, two, three, or four of:

[0874] (1) C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above, —C≡N, —CF₃, C₁-C₃ alkoxy,

[0875] (2) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0876] (3) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0877] (4) —F, Cl, —Br and —I,

[0878] (6) —C₁-C₆ alkoxy optionally substituted with one, two, or threeof —F,

[0879] (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedbelow,

[0880] (8) —OH,

[0881] (9) —C≡N,

[0882] (10) C₃-C₇ cycloalkyl, optionally substituted with one, two orthree substituents selected from the group consisting of —F, —Cl, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl,

[0883] (11) —CO—(C₁-C₄ alkyl),

[0884] (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0885] (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0886] (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zeroR_(1-heteroaryl) is not bonded to the carbon chain by nitrogen,

[0887] (VIII) —(CH₂)_(n-1)—(R_(1-heterocycle)) where n₁ is as definedabove and R_(1-heterocycle) is selected from the group consisting of:

[0888] morpholinyl,

[0889] thiomorpholinyl,

[0890] thiomorpholinyl S-oxide,

[0891] thiomorpholinyl S,S-dioxide,

[0892] piperazinyl,

[0893] homopiperazinyl,

[0894] pyrrolidinyl,

[0895] pyrrolinyl,

[0896] tetrahydropyranyl,

[0897] piperidinyl,

[0898] tetrahydrofuranyl,

[0899] tetrahydrothienyl,

[0900] homopiperidinyl,

[0901] homomorpholinyl,

[0902] homothiomorpholinyl,

[0903] homothiomorpholinyl S,S-dioxide, and

[0904] oxazolidinonyl,

[0905] dihydropyrazolyl

[0906] dihydropyrrolyl

[0907] dihydropyrazinyl

[0908] dihydropyridinyl

[0909] dihydropyrimidinyl

[0910] dihydrofuryl

[0911] dihydropyranyl

[0912] tetrahydrothienyl S-oxide

[0913] tetrahydrothienyl S,S-dioxide

[0914] homothiomorpholinyl S-oxide

[0915] where the R_(1-heterocycle) group is bonded by any atom of theparent R_(1-heterocycle) group substituted by hydrogen such that the newbond to the R_(1-heterocycle) group replaces the hydrogen atom and itsbond, where heterocycle is optionally substituted with one, two, three,or four of:

[0916] (1) C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above, —C≡N, —CF₃, C₁-C₃ alkoxy,

[0917] (2) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0918] (3) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl,

[0919] (4) —F, Cl, —Br and —I,

[0920] (5) C₁-C₆ alkoxy,

[0921] (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three—F,

[0922] (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as definedbelow,

[0923] (8) —OH,

[0924] (9) —C≡N,

[0925] (10) C₃-C₇ cycloalkyl, optionally substituted with one, two orthree substituents selected from the group consisting of —F, —Cl, —OH,—SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl,

[0926] (11) —CO—(C₁-C₄ alkyl),

[0927] (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0928] (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[0929] (14) —SO₂—(C₁-C₄ alkyl),

[0930] (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle)is not bonded to the carbon chain by nitrogen. It is preferred that R₁be —(CH₂)₀₋₁—(R_(1-aryl)) or —(CH₂)_(n1)—(R_(1-heteroaryl)). It is morepreferred that R₁ is —(CH₂)—(R_(1-aryl)) or —(CH₂)—(R_(1-heteroaryl)).It is further preferred that R₁ is —(CH₂)—(R_(1-aryl)) where R_(1-aryl)is phenyl. It is even more preferred that R₁ is —(CH₂)—(R_(1-aryl))where R_(1-aryl) is phenyl substituted with two —F. It is additionallypreferred that the —F substitution is 3,5-difluorobenzyl.

[0931] When R₁ is R_(1-heteroaryl) or R_(1-heterocycle) the bond fromthe R_(1-heteroaryl) or R_(1-heterocycle) group to the —(CH₂)_(n1)—group can be from any ring atom which has an available valence providedthat such bond does not result in formation of a charged species orunstable valence. This means that the R_(1-heteroaryl) orR_(1-heterocycle) group is bonded to —(CH₂)_(n1)— by any ring atom ofthe parent R_(1-heteroary), or R_(1-heterocycle) group which wassubstituted by hydrogen such that the new bond to the R_(1-heteroaryl)or R_(1-heterocycle) group replaces the hydrogen atom and its bond.

[0932] The first step of the process is to protect the free amino groupof the (S)-amino acid (I) with an amino protecting group to produce the(S)-protected amino acid (II) by methods well known to those skilled inthe art. Amino protecting groups are well known to those skilled in theart. See for example, “Protecting Groups in Organic Synthesis”, JohnWiley and sons, New York, N.Y., 1981, Chapter 7; “Protecting Groups inOrganic Chemistry”, Plenum Press, New York, N.Y., 1973, Chapter 2. Thefunction of the amino protecting group is to protect the free aminofunctionality (—NH₂) during subsequent reactions on the (S)-amino acid(I) which would not proceed well, either because the amino group wouldreact and be functionalized in a way that is inconsistent with its needto be free for subsequent reactions, or the free amino group wouldinterfere in the reaction. When the amino protecting group is no longerneeded, it is removed by methods well known to those skilled in the art.By definition the amino protecting group must be readily removable as isknown to those skilled in the art by methods well known to those skilledin the art. Suitable amino PROTECTING GROUP is selected from the groupconsisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl,acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl,difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl,2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl,4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl,3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl,2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl,3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl,4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl,1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl,2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl,cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl,cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl,2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl,2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl,fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl,allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl,5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl,2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl,cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl,isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethylcarbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H. It is preferred that theprotecting group be t-butoxycarbonyl (BOC) and benzyloxycarbonyl (CBZ),it is more preferred that the protecting group be t-butoxycarbonyl. Oneskilled in the art will understand the preferred methods of introducinga t-butoxycarbonyl or benzyloxycarbonyl protecting group and mayadditionally consult T. W. Green and P. G. M. Wuts in “Protective Groupsin Organic Chemistry,” John Wiley and Sons, 1991 for guidance.

[0933] The (S)-protected amino acid (II) is transformed to thecorresponding (S)-protected compound (III) by two different methodsdepending on the nature of R₂ and R₃. R₂ and R₃ are independentlyselected from the group consisting of:

[0934] (I) —H,

[0935] (II) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[0936] (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl)where R_(1-aryl) and R_(1-heteroaryl) are as defined above;

[0937] (IV) C₂-C₆ alkenyl with one or two double bonds,

[0938] (V) C₂-C₆ alkynyl with one or two triple bonds,

[0939] (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of —F, —Cl,—OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken togetherwith the carbon to which they are attached to form a carbocycle ofthree, four, five, six, and seven carbon atoms, optionally where onecarbon atom is replaced by a heteroatom selected from the groupconsisting of —O—, —S—, —SO₂—, —NR_(N-2)—, where R_(N-2) is as definedbelow. It is preferred that R₂ and R₃ both be —H. If R₂ and R₃ are notthe same, an additional enantiomeric center is added to the molecule. Ifit is desired that both R₂ and R₃ are —H, then the (S)-protected aminoacid (II) is reacted with diazomethane, as is well known to thoseskilled in the art, followed by reaction with a compound of the formulaH-X₁ to produce the (S)-protected compound (III). X₁ includes —Cl, —Br,—I, —O-tosylate, —O-mesylate, —O-nosylate; it is preferred that —X₁ be—Br or —Cl. Suitable reaction conditions include running the reaction ininert solvents, such as but not limited to ether, tetrahydrofuran andthe like. The reactions from the (S)-protected amino acid (II) to the(S)-protected compound (III) are carried out for a period of timebetween 10 minutes and 1 day and at temperatures ranging from −78degrees to 20-25 degrees C. It is preferred to conduct the reactions fora period of time between 1-4 hours and at temperatures between −30degrees to −10 degrees C. This process adds one methylene group.

[0940] Alternatively, the (S)-protected compounds of formula (III) canbe prepared by first converting the (S)-protected amino acid (II) to acorresponding methyl or ethyl ester, according to methods wellestablished in the art, followed by treatment with a reagent of formulaX₁—C(R₂)(R₃)—X₁ and a strong metal base. The base serves to affect ahalogen-metal exchange, where the —X₁ undergoing exchange is a halogenselected from chlorine, bromine or iodine. The nucleophilic addition tothe ester derivative gives directly the (S)-protected compound (III).Suitable bases include, but are not limited to the alkyllithiumsincluding, for example, sec-butyllithium, n-butyllithium, andt-butyllithium. The reactions are preferably conducted at lowtemperature, such as −78 degrees C. Suitable reaction conditions includerunning the reaction in inert solvents, such as but not limited to,ether, tetrahydrofuran and the like. Where R₂ and R₃ are both hydrogen,then examples of X₁—C(R₂)(R₃)—X₁ include dibromomethane, diiodomethane,chloroiodomethane, bromoiodomethane and bromochloromethane. One skilledin the art knows the preferred conditions required to conduct thisreaction. Furthermore, if R₂ and/or R₃ are not —H, then by the additionof —C(R₂)(R₃)—X₁ to esters of the (S)-protected amino acid (II) toproduce the (S)-protected compound (III), an additional chiral centerwill be incorporated into the product, provided that R₂ and R₃ are notthe same.

[0941] The (S)-protected compound (III) is then reduced by means wellknown to those skilled in the art for reduction of a ketone to thecorresponding secondary alcohol affording the corresponding alcohol(IV). The means and reaction conditions for reducing the (S)-protectedcompound (III) to the corresponding alcohol (IV) include, for example,sodium borohydride, lithium borohydride, borane, diisobutylaluminumhydride, and lithium aluminium hydride. Sodium borohydride is thepreferred reducing agent. The reductions are carried out for a period oftime between 1 hour and 3 days at temperatures ranging from −78 degreesC. to elevated temperature up to the reflux point of the solventemployed. It is preferred to conduct the reduction between −78 degreesC. and 0 degrees C. If borane is used, it may be employed as a complex,for example, borane-methyl sulfide complex, borane-piperidine complex,or borane-tetrahydrofuran complex. The preferred combination of reducingagents and reaction conditions needed are known to those skilled in theart, see for example, Larock, R. C. in Comprehensive OrganicTransformations, VCH Publishers, 1989. The reduction of the(S)-protected compound (III) to the corresponding alcohol (IV) producesthe second chiral center (third chiral center if R₂ and R₃ are not thesame). The reduction of the (S)-protected compound (III) produces amixture of enantiomers at the second center, (S, R/S)-alcohol (IV). Thisenantiomeric mixture is then separated by means known to those skilledin the art such as selective low-temperature recrystallization orchromatographic separation, for example by HPLC, employing commerciallyavailable chiral columns. The enantiomer that is used in the remainderof the process of CHART A is the (S,S)-alcohol (IV) since thisenantiomer will give the desired biologically active anti-Alzheimer(S,R)-substituted amine (X).

[0942] The (S,S)-alcohol (IV) is transformed to the correspondingepoxide (V) by means known to those skilled in the art. Thestereochemistry of the (S)-(IV) center is maintained in forming theepoxide (V). A preferred means is by reaction with base, for example,but not limited to, hydroxide ion generated from sodium hydroxide,potassium hydroxide, lithium hydroxide and the like. Reaction conditionsinclude the use of C₁-C₆ alcohol solvents; ethanol is preferred. Acommon co-solvent, such as for example, ethyl acetate may also beemployed. Reactions are conducted at temperatures ranging from 45degrees C. up to the reflux temperature of the alcohol employed;preferred temperature ranges are between -20 degrees C. and 20-25degrees C.

[0943] The epoxide (V) is then reacted with the appropriatelysubstituted C-terminal amine, R_(C)—NH₂ (VI) by means known to thoseskilled in the art that opens the epoxide to produce the desiredcorresponding enantiomerically pure (S,R)-protected alcohol (VII). Thesubstituted C-terminal amines, R_(C)—NH₂ (VI) of this invention arecommercially available or are known to those skilled in the art and canbe readily prepared from known compounds. R_(C) includes:

[0944] (I) —C₁-C₁₀ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) whereR_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a)and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a)and R_(1-b) are as defined above,

[0945] (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can beoptionally substituted with one, two or three substituents selected fromthe group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N,—CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO—O—(C₁-C₄ alkyl),—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0946] (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y)are

[0947] —H,

[0948] C₁-C₄ alkyl optionally substituted with one or two —OH,

[0949] C₁-C₄ alkoxy optionally substituted with one, two, or three of—F,

[0950] —(CH₂)₀₋₄-C₃-C₇ cycloalkyl,

[0951] C₂-C₆ alkenyl containing one or two double bonds,

[0952] C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-,

[0953] and where R_(C-x) and R_(C-y) are taken together with the carbonto which they are attached to form a carbocycle of three, four, five,six and seven carbon atoms, optionally where one carbon atom is replacedby a heteroatom selected from the group consisting of —O—, —S—, —SO₂—,—NR_(N-2)— and R_(C-aryl) is defined as R_(N-aryl) is defined below;

[0954] (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) whereR_(C-heteroaryl) is defined as R_(N-heteroaryl) is defined above andR_(C-x) and R_(C-y) are as defined above,

[0955] (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-aryl),R_(C-x) and R_(C-y) are as defined above,

[0956] (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) whereR_(C-aryl), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above,

[0957] (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) whereR_(C-heteroaryl), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above,

[0958] (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-hetetoaryl)—R_(C-heteroaryl)where R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above,

[0959] (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) whereR_(C-aryl), R_(C-x) and R_(C-y) are as defined above, andR_(C-heterocycle) is defined as R_(C-heterocycle) is defined below,

[0960] (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle)where R_(C-heteroaryl) R_(C-heterocycle), R_(C-x) and R_(C-y) are asdefined above,

[0961] (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) whereR_(C-heterocycle), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above,

[0962] (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl)where R_(C-heterocycle), R_(C-heteroaryl), R_(C-x) and R_(C-y) are asdefined above,

[0963] (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle)where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above,

[0964] (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) whereR_(C-heterocycle) is defined as R_(1-heterocycle) is defined above, andR_(C-x) and R_(C-y) are as defined above,

[0965] (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) andR_(C-2) are the same or different and are selected from the groupconsisting of:

[0966] (A) —H,

[0967] (B) —C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above,

[0968] (C) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0969] (D) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0970] (E) —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl),

[0971] (F) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of C₁-C₃alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0972] (G) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as definedfor R_(i-aryl),

[0973] (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is asdefined above,

[0974] (I) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) isas defined above,

[0975] (J) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above,

[0976] (K) —R_(C-heterocycle) where R_(C-heterocycle) is as definedabove,

[0977] (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—,—S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, and where R_(C′-aryl) isdefined above,

[0978] (N) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) andR_(C-heteroaryl) are as defined above,

[0979] (O) —R_(C′-aryl) where R_(C′-aryl) is as defined above, and whereR_(C-3) is the same or different and is:

[0980] (A) —H,

[0981] (B) —C₁-C₆ alkyl optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b)where R_(1-a) and R_(1-b) are as defined above,

[0982] (C) C₂-C₆ alkenyl with one or two double bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0983] (D) C₂-C₆ alkynyl with one or two triple bonds, optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0984] (E) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one,two or three substituents selected from the group consisting of C₁-C₃alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0985] (F)—R_(C′-aryl) where R_(C′-aryl) is as defined above,

[0986] (G) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above,

[0987] (H) —R_(C-heterocycle) where R_(C-heterocycle) is as definedabove,

[0988] (I) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as definedabove,

[0989] (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is asdefined above,

[0990] (K) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) isas defined above,

[0991] (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or differentand are as defined above,

[0992] (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the sameor different and are as defined above,

[0993] (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)) where R_(C-aryl) andR_(C-heteroaryl) are as defined above,

[0994] (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused toR_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) orR_(C-heteroaryl) or R_(C-heterocycle) are as defined above where onecarbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionallyreplaced with NH, NR_(N-5), O, S(═O)₀₋₂, and where cyclopentyl,cyclohexyl, or -cycloheptyl can be optionally substituted with one ortwo -C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, ═O,—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above,

[0995] (XX) C₂-C₁₀ alkenyl containing one or two double bonds optionallysubstituted with one, two or three substituents selected from the groupconsisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are asdefined above,

[0996] (XXI) C₂-C₁₀ alkynyl containing one or two triple bondsoptionally substituted with one, two or three substituents selected fromthe group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N,—CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) andR_(1-b) are as defined above,

[0997] (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-aryl) where R_(C-aryl) isas defined above and R_(C-6) is —(CH₂)₀₋₆—OH,

[0998] (XXII) —(CH₂)₀₋₁—(CHR_(C-6)—(CH₂)₀₋₁—R_(C-heteroaryl) whereR_(C-heteroaryl) and R_(C-6) is as defined above,

[0999] (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl))—CO—O(C₁-C₄ alkyl)where R_(C-aryl) and R_(C-heteroaryl) are as defined above,

[1000] (XXIV) —CH(—CH₂—OH)—CH(—OH)-phenyl-NO₂,

[1001] (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH,

[1002] (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂,

[1003] (XXVIII) —H,

[1004] (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) andR_(1-b) are as defined above.

[1005] It is preferred that R_(C) is:

[1006] —C₁-C₈ alkyl,

[1007] —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl,

[1008] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl),

[1009] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl),

[1010] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle),

[1011] -cyclopentyl or -cyclohexyl ring fused to R_(C-aryl) orR_(C-heteroaryl) or R_(C-heterocycle).

[1012] It is more preferred that R_(C) is:

[1013] —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl,

[1014] —(CR_(C-x)R_(C-y))₀₋₄R_(C-aryl),

[1015] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl),

[1016] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle),

[1017] -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) orR_(C-heteroaryl) or R_(C-heterocycle).

[1018] It is even more preferred that R_(C) is:

[1019] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl),

[1020] -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) orR_(C-heteroaryl) or R_(C-heterocycle).

[1021] It is still more preferred that R_(C) is selected from the groupconsisting of:

[1022] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-aryl) is phenyl,

[1023] —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl),

[1024] -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) orR_(C-heteroaryl) or R_(C-heterocycle). Further, it is preferred thatwhen R_(C) is phenyl, it is substituted in the 3-position or3,5-positions.

[1025] Suitable reaction conditions for opening the epoxide (V) includerunning the reaction in a wide range of common and inert solvents. C₁-C₆alcohol solvents are preferred and isopropyl alcohol most preferred. Thereactions can be run at temperatures ranging from 20-25 degrees C. up tothe reflux temperature of the alcohol employed. The preferredtemperature range for conducting the reaction is between 50 degrees C.up to the reflux temperature of the alcohol employed. When thesubstituted C-terminal amine (VI) is a 1-amino-3,5-cis-dimethylcyclohexyldicarboxylate it is preferrably prepared as follows. Todimethyl-5-aminoisophthalate in acetic acid and methanol, is addedrhodium in alumina in a high-pressure bottle. The bottle is saturatedwith hydrogen at 55 psi and shaken for one week of time. The mixture isthen filtered through a layer of diatomaceous earth and rinsed withmethanol three times, the solvents are removed under reduced pressure(with heat) to give a concentrate. The concentrate is triturated withether and filtered again to give the desired C-terminal amine (VI). Whenthe substituted C-terminal amine (VI) is 1-amino-3,5-cis-dimethoxycyclohexane it is prepared by following the general procedure above andmaking non-critical variations but starting wth 3,5-dimethoxyaniline.When the substituted C-terminal amine (VI) is an aminomethyl group wherethe substituent on the methyl group is an aryl group, for exampleNH₂—CH₂R_(C-aryl), and NH₂—CH₂—R_(C-aryl) is not commercially availableit is preferrably prepared as follows. A suitable starting material isthe (appropriately substituted) aralkyl compound. The first step isbromination of the alkyl substitutent via methods known to those skilledin the art, see for example R. C. Larock in Comprehensive OrganicTransformations, VCH Publishers, 1989, p.313. Next the alkyl halide isreacted with azide to produce the aryl-(alkyl)-azide. Last the azide isreduced to the corresponding amine by hydrogen/catalyst to give theC-terminal amine (VI) of formula NH₂—CH₂—R_(C-aryl). The suitablyfunctionalized C-terminal amines (VI) may readily be prepared by oneskilled in the art via known methods in the literature, makingnon-significant modifications. Select literature references include 1)Calderwood, et al., Tet. Lett., 1997, 38, 1241, 2) Ciganek, J. Org.Chem., 1992, 57,4521, 3) Thurkauf, et al., J. Med. Chem., 1990, 33,1452, 4) Werner, et al., Org. Syn., Coil. Vol. 5, 273, 5) J. Med. Chem.,1999, 42, 4193, 6) Chem. Rev. 1995, 95, 2457, 7) J. Am. Chem. Soc.,1986, 3150, 8) Felman et al., J. Med. Chem., 1992, 35, 1183, 9) J. Am.Chem. Soc. 1970, 92, 3700, 10) J. Med. Chem.,1997, 40, 2323.

[1026] CHART B discloses an alternative process for production of theenantiomerically pure (S,R)-protected alcohol (VII) from the(S)-protected compound (III). In the alternative process, the(S)-protected compound (III) is first reacted with the appropriatelysubstituted C-terminal amine R_(C)—NH₂ (VI) using the preferredconditions described above to produce the corresponding (S)-protectedketone (XI) which is then reduced using the preferred conditionsdescribed above to produce the corresponding (S,R)-protected alcohol(VII).

[1027] CHART C discloses another alternative process for production ofenantiomerically pure (S,R)-protected alcohol (VII) but this time fromthe epoxide (V). In the process of CHART C, the epoxide (V) is reactedwith azide to produce the corresponding enantiomerically pure(S,R)-protected azide (XII). Conditions to conduct the azide mediatedepoxide opening are known to those skilled in the art, see for example,J. March, Advanced Organic Chemistry, 3^(rd) Edition, John Wiley & SonsPublishers, 1985, p. 380. Next, the (S,R)-protected azide (XII) isreduced to the corresponding protected amine (XIII) by methods known tothose skilled in the art. Preferred reducing conditions to reduce the(S,R)-protected azide (XII) in the presence of a t-butoxycarbonylN-protecting group include catalytic hydrogenation, the conditions forwhich are known to those skilled in the art. Alternative reducingconditions which may be used to avoid N-deprotection with protectinggroups other than t-butoxycarbonyl are known to those skilled in theart, see for example, R.C. Larock in Comprehensive OrganicTransformations, VCH Publishers, 1989, p. 409.

[1028] The (S,R)-protected alcohol (VII) is deprotected to thecorresponding (S,R)-amine (VIII) by means known to those skilled in theart for removal of amine protecting group. Suitable means for removal ofthe amine protecting group depends on the nature of the protectinggroup. Those skilled in the art, knowing the nature of a specificprotecting group, know which reagent is preferable for its removal. Forexample, it is preferred to remove the preferred protecting group, BOC,by dissolving the (S,R)-protected alcohol (VII) in a trifluoroaceticacid/dichloromethane mixture. When complete, the solvents are removedunder reduced pressure to give the corresponding (S,R)-amine (as thecorresponding salt, i.e. trifluoroacetic acid salt) which is usedwithout further purification. However, if desired, the (S,R)-amine canbe purified further by means well known to those skilled in the art,such as for example, recrystallization. Further, if the non-salt form isdesired that also can be obtained by means known to those skilled in theart, such as for example, preparing the free base amine via treatment ofthe salt with mild basic conditions. Additional BOC deprotectionconditions and deprotection conditions for other protecting groups canbe found in T. W. Green and P. G. M. Wuts in “Protective Groups inOrganic Chemistry,” John Wiley and Sons, 1991, p. 309. Typicalchemically suitable salts include trifluoroacetate, and the anion ofmineral acids such as chloride, sulfate, phosphate; preferred istrifluoroacetate and chloride.

[1029] The (S,R)-amine (VIII) is then reacted with an appropriatelysubstituted amide forming agent (IX) such as anhydride, acyl halide, oracid of the formula (R_(N-1)—X_(N))₂O or R_(N-1)—X_(N)—X₂ orR_(N-1)—X_(N)—OH (IX) by nitrogen-acylation means known to those skilledin the art to produce the corresponding (S,R)-substituted amine (X).Nitrogen acylation conditions for reaction of the (S,R)-amine (VIII)with an amide forming agent (IX) to produce the corresponding(S,R)-substituted amine (X) are known to those skilled in the art andcan be found in R. C. Larock in Comprehensive Organic Transformations,VCH Publishers, 1989, p. 981, 979, and 972. R_(N) includes:

[1030] (I) R_(N-1)—X_(N)— where X_(N) is selected from the groupconsisting of:

[1031] (A) —CO—,

[1032] (B) —SO₂—,

[1033] (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are—H and C₁-C₄ alkyl,

[1034] (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from thegroup consisting of —O—, —S— and —NR′— and where R′ and R″ are asdefined above,

[1035] (E) a single bond;

[1036] where R_(N-1) is selected from the group consisting of:

[1037] (A) R_(N-aryl) where R_(N) aryl is phenyl, 1-naphthyl,2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted withone, two or three of the following substituents which can be the same ordifferent and are:

[1038] (1) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[1039] (2) —OH,

[1040] (3) —NO₂,

[1041] (4) —F, —Cl, —Br, —I,

[1042] (5) —CO—OH,

[1043] (6) —C≡N,

[1044] (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are selected from the group consisting of:

[1045] (a) —H,

[1046] (b) —C₁-C₆ alkyl optionally substituted with one substitutentselected from the group consisting of:

[1047] (i) —OH,

[1048] (ii) —NH₂,

[1049] (c) —C₁-C₆ alkyl optionally substituted with one, two or three—F, —Cl, —Br, —I,

[1050] (d) —C₃-C₇ cycloalkyl,

[1051] (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl),

[1052] (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl),

[1053] (g) —C₂-C₆ alkenyl with one or two double bonds,

[1054] (h) —C₂-C₆ alkynyl with one or two triple bonds,

[1055] (i) —C₁-C₆ alkyl chain with one double bond and one triple bond,

[1056] (j) —R_(1-aryl) where R_(1-aryl) is as defined above,

[1057] (k) —R_(1-heteroary), where R_(1-heteroaryl) is as defined above,

[1058] (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),

[1059] (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three doublebonds),

[1060] (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triplebonds),

[1061] (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl),

[1062] (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as definedabove,

[1063] (13) —CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is asdefined above,

[1064] (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above,

[1065] (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from thegroup consisting of morpholinyl, thiomorpholinyl, piperazinyl,piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinylS-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinylwhere each group is optionally substituted with one, two, three, or fourof C₁-C₆ alkyl,

[1066] (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from thegroup consisting of:

[1067] (a) C₁-C₆ alkyl,

[1068] (b) —(CH₂)₀₋₂—(R₁aryl) where R_(1-aryl) is as defined above,

[1069] (c) C₂-C₆ alkenyl containing one or two double bonds,

[1070] (d) C₂-C₆ alkynyl containing one or two triple bonds,

[1071] (e) C₃-C₇ cycloalkyl,

[1072] (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is asdefined above,

[1073] (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) areas defined above,

[1074] (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl),

[1075] (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl),

[1076] (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl),

[1077] (21) —(CH₂)₀₋₄N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can bethe same or different and is as defined above,

[1078] (22) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—N(R_(N-5))₂, where R_(N-5) canbe the same or different and is as defined above,

[1079] (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same ordifferent and is as defined above,

[1080] (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as defined above,

[1081] (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can bethe same or different and are as defined above,

[1082] (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above,

[1083] (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),

[1084] (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —Hor C₁-C₄ alkyl,

[1085] (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[1086] (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[1087] (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above,

[1088] (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as definedabove,

[1089] (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above,

[1090] (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one,two, three, four or five of —F),

[1091] (35) C₃-C₇ cycloalkyl,

[1092] (36) C₂-C₆ alkenyl with one or two double bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[1093] (37) C₂-C₆ alkynyl with one or two triple bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[1094] (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) andR_(N-2) can be the same of different and are as described above,

[1095] (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl,

[1096] (B) —R_(N-heteroaryl) where R_(N-heteroaryl) is selected from thegroup consisting of:

[1097] pyridinyl,

[1098] pyrimidinyl,

[1099] quinolinyl,

[1100] benzothienyl,

[1101] indolyl,

[1102] indolinyl,

[1103] pryidazinyl,

[1104] pyrazinyl,

[1105] isoindolyl,

[1106] isoquinolyl,

[1107] quinazolinyl,

[1108] quinoxalinyl,

[1109] phthalazinyl,

[1110] imidazolyl,

[1111] isoxazolyl,

[1112] pyrazolyl,

[1113] oxazolyl,

[1114] thiazolyl,

[1115] indolizinyl,

[1116] indazolyl,

[1117] benzothiazolyl,

[1118] benzimidazolyl,

[1119] benzofaranyl,

[1120] furanyl,

[1121] thienyl,

[1122] pyrrolyl,

[1123] oxadiazolyl,

[1124] thiadiazolyl,

[1125] triazolyl,

[1126] tetrazolyl,

[1127] oxazolopyridinyl,

[1128] imidazopyridinyl,

[1129] isothiazolyl,

[1130] naphthyridinyl,

[1131] cinnolinyl,

[1132] carbazolyl,

[1133] beta-carbolinyl,

[1134] isochromanyl,

[1135] chromanyl,

[1136] tetrahydroisoquinolinyl,

[1137] isoindolinyl,

[1138] isobenzotetrahydrofuranyl,

[1139] isobenzotetrahydrothienyl,

[1140] isobenzothienyl,

[1141] benzoxazolyl,

[1142] pyridopyridinyl,

[1143] benzotetrahydrofuranyl,

[1144] benzotetrahydrothienyl,

[1145] purinyl,

[1146] benzodioxolyl,

[1147] triazinyl,

[1148] phenoxazinyl,

[1149] phenothiazinyl,

[1150] pteridinyl,

[1151] benzothiazolyl,

[1152] imidazopyridinyl,

[1153] imidazothiazolyl,

[1154] dihydrobenzisoxazinyl,

[1155] benzisoxazinyl,

[1156] benzoxazinyl,

[1157] dihydrobenzisothiazinyl,

[1158] benzopyranyl,

[1159] benzothiopyranyl,

[1160] coumarinyl,

[1161] isocoumarinyl,

[1162] chromonyl,

[1163] chromanonyl,

[1164] pyridinyl-N-oxide,

[1165] tetrahydroquinolinyl

[1166] dihydroquinolinyl

[1167] dihydroquinolinonyl

[1168] dihydroisoquinolinonyl

[1169] dihydrocoumarinyl

[1170] dihydroisocoumarinyl

[1171] isoindolinonyl

[1172] benzodioxanyl

[1173] benzoxazolinonyl

[1174] pyrrolyl N-oxide,

[1175] pyrimidinyl N-oxide,

[1176] pyridazinyl N-oxide,

[1177] pyrazinyl N-oxide,

[1178] quinolinyl N-oxide,

[1179] indolyl N-oxide,

[1180] indolinyl N-oxide,

[1181] isoquinolyl N-oxide,

[1182] quinazolinyl N-oxide,

[1183] quinoxalinyl N-oxide,

[1184] phthalazinyl N-oxide,

[1185] imidazolyl N-oxide,

[1186] isoxazolyl N-oxide,

[1187] oxazolyl N-oxide,

[1188] thiazolyl N-oxide,

[1189] indolizinyl N-oxide,

[1190] indazolyl N-oxide,

[1191] benzothiazolyl N-oxide,

[1192] benzimidazolyl N-oxide,

[1193] pyrrolyl N-oxide,

[1194] oxadiazolyl N-oxide,

[1195] thiadiazolyl N-oxide,

[1196] triazolyl N-oxide,

[1197] tetrazolyl N-oxide,

[1198] benzothiopyranyl S-oxide,

[1199] benzothiopyranyl S,S-dioxide,

[1200] where the R_(N-heteroaryl) group is bonded by any atom of theparent R_(N-heteroaryl) group substituted by hydrogen such that the newbond to the R_(N-heteroaryl) group replaces the hydrogen atom and itsbond, where heteroaryl is optionally substituted with one, two three, orfour of:

[1201] (1) C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above,

[1202] (2) —OH,

[1203] (3) —NO₂,

[1204] (4) —F, —Cl, —Br, —I,

[1205] (5) —CO—OH,

[1206] (6) —C═N,

[1207] (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are selected from the group consisting of:

[1208] (a) —H,

[1209] (b) —C₁-C₆ alkyl optionally substituted with one substitutentselected from the group consisting of:

[1210] (i) —OH,

[1211] (ii) —NH₂,

[1212] (c) —C₁-C₆ alkyl optionally substituted with one to three —F,—Cl, —Br, —I,

[1213] (d) —C₃-C₇ cycloalkyl,

[1214] (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl),

[1215] (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl),

[1216] (g) —C₂-C₆ alkenyl with one or two double bonds,

[1217] (h) —C₂-C₆ alkynyl with one or two triple bonds,

[1218] (i) —C₁-C₆ alkyl chain with one double bond and one triple bond,

[1219] (j) —R_(1-aryl) where R_(1-aryl) is as defined above,

[1220] (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above,

[1221] (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl),

[1222] (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three doublebonds),

[1223] (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triplebonds),

[1224] (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl),

[1225] (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as definedabove,

[1226] (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is asdefined above,

[1227] (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is asdefined above,

[1228] (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from thegroup consisting of morpholinyl, thiomorpholinyl, piperazinyl,piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinylS-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinylwhere each group is optionally substituted with one, two, three, or fourof C₁-C₆ alkyl,

[1229] (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from thegroup consisting of:

[1230] (a) C₁-C₆ alkyl,

[1231] (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above,

[1232] (c) C₂-C₆ alkenyl containing one or two double bonds,

[1233] (d) C₂-C₆ alkynyl containing one or two triple bonds,

[1234] (e) C₃-C₇ cycloalkyl,

[1235] (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is asdefined above,

[1236] (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) areas defined above,

[1237] (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl),

[1238] (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl),

[1239] (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl),

[1240] (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can bethe same or different and is as defined above,

[1241] (22) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—N(R_(N-5))₂, where R_(N-5) canbe the same or different and is as defined above,

[1242] (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same ordifferent and is as defined above,

[1243] (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as defined above,

[1244] (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can bethe same or different and are as defined above,

[1245] (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above,

[1246] (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl),

[1247] (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —Hor C₁-C₄ alkyl,

[1248] (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[1249] (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as definedabove,

[1250] (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above,

[1251] (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as definedabove,

[1252] (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above,

[1253] (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one,two, three, four, or five of —F),

[1254] (35) C₃-C₇ cycloalkyl,

[1255] (36) C₂-C₆ alkenyl with one or two double bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[1256] (37) C₂-C₆ alkynyl with one or two triple bonds optionallysubstituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃,C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove,

[1257] (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) andR_(N-2) can be the same or different and are as described above,

[1258] (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl,

[1259] (C) R_(N-aryl)—W—R_(N-aryl),

[1260] (D) R_(N-aryl)—W—R_(N-heteroaryl),

[1261] (E) R_(Naryl)—W—R_(N-1-heterocycle) where R_(N-heterocycle) isdefined as R_(1-heterocycle) is defined above,

[1262] (F) R_(N-heteroaryl)—W—R_(N-aryl),

[1263] (G) R_(N-heteroaryl)—W—R_(N-heteroaryl),

[1264] (H) R_(N-heteroaryl)—W—R_(N-1-heterocycle), whereR_(N-1-heterocycle) is defined as R_(1-heterocycle) is defined above,

[1265] (I) R_(N-heterocycle)—W—R_(N-aryl),

[1266] (J) R_(N-heterocycle)—W—R_(N-heteroaryl),

[1267] (K) R_(N-heterocycle)—W—R_(N-1-heterocycle),

[1268] where W is

[1269] (1) —(CH₂)₀₋₄—,

[1270] (2) —O—,

[1271] (3) —S(O)₀₋₂—,

[1272] (4) —N(R_(N-5))— where R_(N-5) is as defined above, or

[1273] (5) —CO—;

[1274] (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substitutedwith one two, or three substitutents selected from the group consistingof:

[1275] (A) —OH,

[1276] (B) —C₁-C₆ alkoxy,

[1277] (C) —C₁-C₆ thioalkoxy,

[1278] (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl,

[1279] (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[1280] (F) —CO—R_(N-4) where R_(N-4) is as defined above,

[1281] (G) —SO₂—(C₁-C₈ alkyl),

[1282] (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the sameor different and are as defined above,

[1283] (I) —NH—CO—(C₁-C₆ alkyl),

[1284] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[1285] (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[1286] (L) —R_(N-4) where R_(N-4) is as defined above,

[1287] (M) —O—CO—(C₁-C₆ alkyl),

[1288] (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same ordifferent and are as defined above,

[1289] (O) —O—(C₁-C₅ alkyl)—COOH,

[1290] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof: —F, —Cl, —Br, —I),

[1291] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[1292] (R) —F, —Cl,

[1293] (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl is optionallysubstituted with one, two, or three substitutents selected from thegroup consisting of:

[1294] (A) —OH,

[1295] (B) —C₁-C₆ alkoxy,

[1296] (C) —C₁-C₆ thioalkoxy,

[1297] (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl,

[1298] (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[1299] (F) —CO—RN₄ where R_(N-4) is as defined above,

[1300] (G) —SO₂—(C₁-C₈ alkyl),

[1301] (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the sameor different and are as defined above,

[1302] (I) —NH—CO—(C₁-C₆ alkyl),

[1303] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[1304] (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[1305] (L) —R_(N-4) where R_(N-4) is as defined above,

[1306] (M) —O—CO—(C₁-C₆ alkyl),

[1307] (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same ordifferent and are as defined above,

[1308] (O) —O—(C₁-C₅ alkyl)—COOH,

[1309] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof: —F, —Cl, —Br, —I),

[1310] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[1311] (R) —F, —Cl,

[1312] (IV) —CO—(C₁-C₆ alkyl)—S—(C₁-C₆ alkyl) where alkyl is optionallysubstituted with one, two, or three substitutents selected from thegroup consisting of:

[1313] (A) —OH,

[1314] (B) —C₁-C₆ alkoxy,

[1315] (C) —C₁-C₆ thioalkoxy,

[1316] (D) —CO—O—R_(N-8) where R_(N-8) is as defined above,

[1317] (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[1318] (F) —CO—R_(N-4) where R_(N-4) is as defined above,

[1319] (G) —SO₂—(C₁-C₈ alkyl),

[1320] (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the sameor different and are as defined above,

[1321] (I) —NH—CO—(C₁-C₆ alkyl),

[1322] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[1323] (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same ordifferent and are as defined above,

[1324] (L) —R_(N-4) where R_(N-4) is as defined above,

[1325] (M) —O—CO—(C₁-C₆ alkyl),

[1326] (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same ordifferent and are as defined above,

[1327] (O) —O—(C₁-C₅ alkyl)—COOH,

[1328] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof: —F, —Cl, —Br, —I),

[1329] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[1330] (R) —F, —Cl,

[1331] (V)—CO—CH(—(CH₂)₀₋₂—O—R_(N-10))—CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)) whereR_(N-aryl) and R_(N-heteroaryl) are as defined above, where R_(N-10) isselected from the group consisting of:

[1332] (A) —H,

[1333] (B) C₁-C₆ alkyl,

[1334] (C) C₃-C₇ cycloalkyl,

[1335] (D) C₂-C₆ alkenyl with one double bond,

[1336] (E) C₂-C₆ alkynyl with one triple bond,

[1337] (F) R_(1-aryl) where R_(1-aryl) is as defined above,

[1338] (G) R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above,

[1339] (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substitutedwith one or two substitutents selected from the group consisting of:

[1340] (A) —(CH₂)₀₋₄—OH,

[1341] (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy,

[1342] (C) —(CH₂)₀₋₄-C₁-C₆ thioalkoxy,

[1343] (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or-phenyl,

[1344] (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are as defined above,

[1345] (F) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is as defined above,

[1346] (G) —(CH₂)₀₋₄—SO₂—(C₁-C₈ alkyl),

[1347] (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) arethe same or different and are as defined above,

[1348] (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl),

[1349] (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above,

[1350] (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are thesame or different and are as defined above,

[1351] (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above,

[1352] (M) —O—CO—(C₁-C₆ alkyl),

[1353] (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same ordifferent and are as defined above;

[1354] (O) —O—(C₁-C₅ alkyl)—COOH,

[1355] (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or threeof: —F, —Cl, —Br, —I),

[1356] (Q) —NH—SO₂—(C₁-C₆ alkyl),

[1357] (R) —F, —Cl.

[1358] It is preferred that R_(N) is selected from the group consistingof:

[1359] R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl)or R_(N-heteroaryl) where R_(N-aryl) is phenyl where the substitution onphenyl is 1,3-, and where R_(N-aryl) or R_(N-heteroaryl) are substitutedwith one —CO—NR_(N-2)R_(N-3),

[1360] R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N) arylor R_(N-heteroaryl) where R_(N-aryl) is phenyl substituted with one C₁alkyl where the substitution on the phenyl is 1,3,5-, and whereR_(N-aryl) or R_(N-heteroaryl) are substituted with one—CO—NR_(N-2)R_(N-3),

[1361] R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) isR_(N-heteroaryl) where R_(N-heteroaryl) is substituted with one—CO—NR_(N-2)R_(N-3) It is further preferred that R_(N-2) and R_(N-3) arethe same and are C₃ alkyl. It is further preferred that:

[1362] R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl)where R_(N-aryl) is phenyl substituted with one —CO—NR_(N-2)R_(N-3)where the substitution on phenyl is 1,3-,

[1363] R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl)where R_(N-aryl) is phenyl substituted with one C₁ alkyl and with one—CO—NR_(N-2)R_(N-3) where the substitution on the phenyl is 1,3,5-. Itis preferred that X_(N) is (A) —CO— and (B) —SO₂—; it is more preferredthat X_(N) be —CO—. X₂ includes —Cl, —Br; it is preferred that X₂ is—Cl.

[1364] The nitrogen-acylation of primary amines to produce secondaryamides is one of the oldest known reactions. The amide forming agents,(R_(N-1)—X_(N))₂O or R_(N-1)—X_(N)—X₂ or R_(N-1)—X_(N)—OH (IX) are knownto those skilled in the art and are commercially available or can bereadily prepared from known starting materials by methods known in theliterature. It is preferred to use an isophthalic acid acylating agent(IX) of the formula R_(N-2)R_(N-3)N—CO-phenyl-CO— or a methylisophthalicacid acylating agent (IX) of the formulaR_(N-2)R_(N-3)N—CO—(CH₃—)phenyl-CO— where the substitution is5-methyl-1,3-isophthalic acid. The more preferred5-methyl-1,3-isophthalic acid is3-[(N,N-dipropylamino)carbonyl]-5-methylbenzoic acid (IX). Thesecompounds are preferably prepared as follows. An ester, preferably themonomethyl ester of isophthalic acid or methyl 5-methyl-1,3-isophthalateis dissolved in a THF/DMF mixture. 1,1′-Carbonyldiimidazole is added at20-25 degrees C. Next the desired amine (H-NR_(N-2)R_(N-3)) is added.After 3-24 hr of stirring at 20 degrees C. to the reflux temperature ofthe solvent, the reaction mixture is partitioned between saturatedaqueous ammonium chloride and a water immiscible organic solvent such asethyl acetate. The aqueous layer is separated and extracted twice morewith the organic solvent (ethyl acetate). The organic extracts arecombined and then washed with saturated aqueous solutions of bicarbonateand saline and dried over anhydrous sodium sulfate or magnesium sulfate.Filtration of the drying agent and removal of solvents by reducedpressure gives the methyl ester of the desiredR_(N-2)R_(N-3)N—CO-phenyl-CO—O—CH₃ or a methylisophthalic acid acylatingagent (IX) R_(N-2)R_(N-3)N—CO—(CH₃-)phenyl-CO—O—CH₃. Purification of the(methyl) ester can be achieved via chromatography on silica gel elutingwith ethyl acetate in hexanes. The isophthalate ester ormethylisophthalate ester of the mono-alkyl or di-alkyl amide is thentreated with an aqueous solution of base such as lithium hydroxide in aminimum amount of THF/methanol/water and stirred 3-24 hours at 20degrees C. to the reflux temperature of the solvent. The solvents arethen removed under reduced pressure and subsequently partitioned betweenwater and a water immiscible solvent such as ethyl acetate, for example.If emulsions prohibit separation of the two phases, a small amount ofsaline is added to aid in separation. The aqueous phase is separated andextracted once more with a water immiscible solvent such as ethylacetate, for example. The aqueous phase is then acidified withconcentrated acid, preferably hydrochloric until pH ≦3. The mixtureobtained is then extracted three times with a water immiscible solventsuch as ethyl acetate, for example. These combined organic extracts aredried over anhydrous sodium or magnesium sulfate. The drying agent isremoved by filtration and the organic solvent is removed under reducedpressure to give product. The mono- or di-alkyl amideisophthalate/methylisophthalate is used as such in the next reactionwith the (S,R)-amine (VIII) to produce the (S,R)-substituted amine (X).

[1365] When it is desired to produce a primary amide, R_(N-2) andR_(N-3) are both —H, the following procedure is preferred. An ester,preferably the methyl ester of isophthalate or methyl5-methyl-1,3-isophthalate is dissolved in a THF/DMF mixture. CDI isadded at 20-25 degrees C. After five to thirty minutes, ammonia gas isbubbled into the mixture through a syringe needle for 1 hr. The mixtureis cooled to 0 degrees C. for the duration of the hour. The reaction isleft stirring under a balloon of ammonia overnight at 20-25 degrees C.,after which time the reaction mixture is partitioned between saturatedaqueous ammonium chloride and a water immiscible solvent such as ethylacetate, for example. The phases are separated and the aqueous phase isextracted twice more with ethyl acetate. The organic extracts are washedwith saturated aqueous solutions of bicarbonate and saline and driedover anhydrous sodium or magnesium sulfate. Filtration of the dryingagent and removal of solvents under reduced pressure gives the ester ofthe desired isophthalic acid or the isophthalic acid acylating agent(IX). Purification of the (methyl) ester can be achieved viachromatography on silica gel eluting with isopropanol/chloroform. Theisophthalate ester or methylisophthalate ester of the primary amide isthen treated with an aqueous solution of base such as lithium hydroxidein a minimum amount of THF/methanol/water and stirred overnight at 20-25degrees C. after which time the solvents are removed under reducedpressure and subsequently partitioned between water and a waterimmiscible solvent such as ethyl acetate, for example. If emulsionsprohibit separation of the two phases, a small amount of saline is addedto aid in separation. The aqueous phase is separated and extracted oncemore with a water immiscible solvent such as ethyl acetate, for example.The aqueous phase is then acidified with concentrated acid, preferablyhydrochloric until pH ≦3. The mixture obtained is then extracted threetimes with ethyl acetate. These combined organic extracts are dried overanhydrous sodium or magnesium sulfate. The drying agent is removed byfiltration and the organic solvent removed under reduced pressure togive product. The amide isophthalic acid is used as such in the nextreaction with (VIII) to produce (X).

[1366] When it is desired that the amine be cyclized to be a group suchas morpholinyl, piperazinyl, piperidinyl and pyrrolidinyl, etc thefollowing procedure is preferably followed. An ester, preferably themethyl ester of isophthalic acid or methyl 5-methyl-1,3-isophthalate isdissolved in dry methylene chloride and three drops of DMF are added.The mixture is cooled to 0 degrees C. and then oxalyl chloride is added.The mixture is stirred at 0 degrees C. for 30 minutes to two hours afterwhich the solvents are removed under reduced pressure. The acid chlorideis left under vacuum overnight. The crude acid chloride is dissolved indry methylene and cooled to 0 degrees C. before the addition of thecyclic amine and a tertiary amine base such as N-methyl piperidine, forexample. The reaction mixture is stirred at 0 degrees C for I to 6 hrbefore the solvents are removed under reduced pressure. The residue isdiluted with water and a water immiscible solvent such as ethyl acetate,for example, and the phases are separated. The aqueous phase isextracted twice more with a water immiscible solvent such as ethylacetate, for example, and the combined organic extracts are washed withsaturated aqueous bicarbonate and dried over anhydrous sodium ormagnesium sulfate. Filtration of the drying agent and removal ofsolvents under reduced pressure gives the product cyclic amide. Thecyclic amide is then treated with an aqueous base such as lithiumhydroxide in a minimum amount of THF/methanol/water and stirredovernight at 20-25 degrees C., after which time the solvents are removedunder reduced pressure and the residue is subsequently partitionedbetween water and a water immiscible solvent such as ethyl acetate, forexample. The aqueous phase is extracted once more with ethyl acetate.Removal of water from the aqueous phase under reduced pressure gives thedesired cyclic amide product (IX).

[1367] When it is desired that R_(N-1) is carbocycle, for example butnot limited to, cyclohexane, one may then start with a suitablyfunctionalized dimethyl isophthalate and via methods taught in theliterature (Meyers, A. I., Org. Syn., 1971, 51, 103) one may reduce thesix-membered ring with reducing agents such as rhodium (5%) on aluminain the presence of acetic acid and methanol under a hydrogen atmosphereto afford the corresponding dimethyl cyclohexane dicarboxylate.

[1368] CHART D sets forth an alternative process for production of the(S,R)-substituted amine (X) from the (S,R)-protected azide (XII), whichis produced from the corresponding epoxide (V) in CHART C. The aminoprotecting group is removed to produce the corresponding unprotectedazide (XIV) by methods previously described in CHART A for theconversion of (S,R)-protected alcohol (VII) to the corresponding(S,R)-amine (VIII). The (S,R)-unprotected azide (XIV) is then acylatedon nitrogen to produce the corresponding (S,R)-azide (XV). Next, theazide functionality is reduced as previously discussed for theconversion of the (S,R)-protected azide (XII) to the corresponding(S,R)-protected amine (XIII) to give the (S,R)-free amine (XVI). Last,the (S,R)-free amine (XVI) is transformed to the corresponding(S,R)-substituted amine (X) by nitrogen alkylation with a compound ofthe formula R_(C)—X₃ to give the corresponding (S,R)-substituted amine(X). X₃ is an appropriate leaving group, such as but not limited to,—Cl, —Br, —I, —O-mesylate, —O-tosylate, O-triflate, etc. X₃ may also bean aldehyde; the corresponding coupling with (XVI) via the well knownreductive amination procedure gives the (S,R)-substituted amine (X).

[1369] Carbocylic amide forming agents (IX) are also provided for by theinvention. For example, the carbocyclic amide forming agents of theformula

[1370] (IX) are readily prepared from known starting materials bymethods disclosed in the literature and known to those skilled in theart, for example, J. Med. Chem. 1998, 41, 1581, J Org. Chem. 2000, 65,1305. It is also understood that instead of the carboxylic acid, one mayreadily employ an acyl halide, where the halide is preferably choride,or a suitable group to produce a mixed anhydride; these methods aretaught by CHART A. For additional guidance on the formation ofcarbocyles and preferably cyclopropanes, one may consult M. P. Doyle; M.A. McKervery; T. Ye in Modern Catalytic Methods for Organic Synthesiswith Diazo Compounds From Cyclopropanes to Ylides, Wiley-Interscience,1998, pp. 163-279.

[1371] CHARTs E, F, G, and H disclose various methods to produce theR_(N) portion of the substituted amine (X) where the phenyl ring of theR_(N) 1,3-disubstituted moiety, —CO-phenyl-CO—, is further substitutedin the 5-position with various groups such as amides, nitrites, halides,and amines. These compounds are prepared by methods known to thoseskilled in the art. The process chemistry of each reaction is known tothose skilled in the art. What is novel here is the order of eachprocess step and/or the specific reactants used. One skilled in the artknowing the desired product would know at least one method to preparethe desired product by using known starting materials. Hence, thefollowing discussion is not necessary but is set forth to further aidthose interested in preparing the compounds of the invention.

[1372] CHART E discloses alternate processes for the transformation ofthe aniline (XVII) or acid ester (XVIII) to the corresponding acid(IX-XXIII). One process begins with the commercially available aniline(XVII) where R_(N-a) is preferably —H, C₁-C₄ alkyl or benzyl. Theaniline (XVII) is treated with a diazotizing reagent such as sodium orpotassium nitrite in mineral acid, followed by a halogen source such ascopper (II) halide or alkali metal halide, or by an organic diazotizingreagent such as an alkyl nitrite in a strong acid such as acetic acid ortrifluoroacetic acid, followed by a halide source such as copper (II)halide or alkali metal halide to give the halo acid ester (XIX) whereR_(N-b) is —Cl, —Br or —I. Alternatively, the acid ester (XVIII) istreated with N-halosuccinimide and trifluoromethanesulfonic acid to givethe halo acid ester (XIX). The halo acid ester (XIX) is then convertedto the ester amide (XXI) using a primary or secondary amine of theformula H—NR_(Nalpha)R_(Nbeta) (AMINE) where R_(Nalpha) and R_(Nbeta)are the same or different or can be cyclized. These groups, R_(Nalpha)and R_(Nbeta), become part of the substituted amine (X) and are includedin the definition of R_(N). R_(N) includes R_(N-1)—X_(N)— where thelinker, —X_(N)—, includes —CO— and R_(N-1) includes R_(N-aryl).R_(N-aryl) is defined to include phenyl (-phenyl) optionally substitutedwith two amides:

[1373] —CO—NR_(N-2)R_(N-3) and

[1374] —CO—R_(N-4). R_(Nalpha) and R_(Nbeta) include both the non-cyclicamides, —CO—NR_(N-2)R_(N-3) and the cyclic amides-CO—R_(N-4) whereR_(N-2), R_(N-3) and R_(N-4) are as defined in the claims.Alternatively, the halo acid ester (XIX) is converted to the dihaloester (XX) by methods known to those skilled in the art. R_(N), includes—Cl and —F. The dihalo ester (XX) is treated with a primary or secondaryamine of the formula H-NR_(Nalpha)R_(Nbeta) (AMINE) to give the esteramide (XXI). The ester amide (XXI) is then reacted with an AMINE in acarbon monoxide atmosphere in the presence of a palladium catalyst usingmethods such as those reviewed by Heck, (Palladium Reagents in OrganicSynthesis, 1985 pp. 342-365). to give the diamide (XXII). Hydrolysis ofthe ester portion of the diamide (XXII) using methods well known tothose skilled in the art gives the diamide acid (XXIII).

[1375] In CHART F, an alterate route to intermediate diamide (XXII) isshown starting from commercially available phenol (XXIV). The phenol(XXIV) is treated with a trifluoromethanesulfonating reagent such astrifluoromethanesulfonic anhydride to give triflate (XXV). The triflate(XXV) is reacted under the conditions of palladium catalysis in thepresence of carbon monoxide and an amine of the formulaH-NR_(Nalpha)R_(Nbeta) (AMINE) as for the conversion of the ester amide(XXI) to the corresponding diamide (XXII) in CHART E to give the diester(XXVI). The diester (XXVI) is hydrolyzed using methods known to thoseskilled in the art to give the monoacid (XXVII). The monoacid (XXVII) isthen converted to the diamide (XXII) using conditions such as for theconversion of the halo acid ester (XIX) to the ester amide (XXI) inCHART E.

[1376] CHART G discloses another route to prepare the ester amide (XXI).The reaction starts with commercially available nitro compound (XXVIII)which is condensed with an (AMINE) using coupling methods known to thoseskilled in the art to give the nitro amide (XXX). The nitro amide (XXX)can also be prepared by first treating the nitro compound (XXVIII) withreagents such as thionyl chloride, or DMF and oxalyl chloride, or othermethods known to those skilled in the art to give the acid chloride(XXIX), which upon treatment with the (AMINE) gives the nitro amide(XXX). Reduction of the nitro amide (XXX) using methods known to thoseskilled in the art (see, for example, Smith and March, Advanced OrganicChemistry, 5^(th) ed.) gives amide aniline (XXXI). The amide aniline(XXXI) is then treated with diazotizing reagents such as sodium orpotassium nitrite in mineral acid, followed by a halogen source such ascopper (II) halide or alkali metal halide, or by an organic diazotizingreagent such as an alkyl nitrite in a strong acid such as acetic acid ortrifluoroacetic acid, followed by a halide source such as copper (II)halide or alkali metal halide to give the ester amide (XXI).

[1377] CHART H discloses a process to prepare the diamide acid(IX-XXIII) from the ester amide (XXI), where one of the amides isunsubstituted and is —CO—NH₂. This process starts from either the esteror the acid, for example the ester amide (XXI) is treated with copper(I) cyanide (CuCN) in N-methylpyrrolidinone or DMF, preferablyN-methylpyrrolidinone, to give the nitrite (XXXII). The nitrile (XXXII)is converted to the primary amide (XXXIII) using urea-hydrogen peroxidecomplex (see Synth. Commun. (1993) 3149) or the methods of Synth.Commun. (1990) 1445, Synth. Commun. (1997) 3119, J Org. Chem. (1992)2521, Tet. Lett. (1996) 6555, Ind. J. Chem., Sect. B, (1999) 974, Tet.Lett. (1995) 3469, Tet. Lett. (1998) 3005, or others. When the esteramide (XXI) is in the form of an ester, an additional hydrolysis stepusing lithium hydroxide, sodium hydroxide, potassium hydroxide, bariumhydroxide, or other hydrolysis methods known to those skilled in the artis used to convert the diamide ester (XXXIII) to the diamide acid(IX-XXIII).

[1378] CHART I discloses an alternate synthetic route from the protectedalcohol (VII) to the substituted amine (X) which uses a diprotectedintermediate (XXXIV) whereby the nitrogen atom attached to the R_(C)substitutent is protected. Using the process of CHART I, the monoprotected alcohol (VII) is reacted with a new protecting group to formthe orthogonally protected (XXXIV). This is a common strategy employedin traditional peptide chemistry by those skilled in the art, see M.Bodansky, Principles of Peptide Chemistry. When the mono protectedalcohol (VII) is protected with CBZ one skilled in the art could reactit with either (BOC)₂O in methylene chloride or similar organic solventor FMOC—Cl in methylene chloride or similar organic solvent to prepareorthogonally protected (XXXIV). Then the CBZ group is removed byhydrogenation in the presence of a catalytic amount of palladium oncarbon in an alcoholic solvent, such as methanol, or ethyl acetate, orwith catalytic palladium on carbon in alcoholic solvents in the presenceof ammonium formate as is known to those skilled in the art. This givesthe R_(C)—N protected (XXXV). Similarly, when the mono protected alcohol(VII) is protected as a BOC it can be reacted with CBZ—Cl underSchotten-Bauman conditions or CBZ—OSu in THF to prepare the reversed(XXXIV). Then the BOC group can be cleaved with hydrochloric acid (4 N)in methanol, ethanol or dioxane or with trifluoroacetic acid inmethylene chloride or by other methods such as those described in ThePeptides, Analysis, Synthesis, Biology, Vol. 3, Ed. E. Gross and J.Meienhofer (1981) to liberate the CBZ R_(C)—N protected (XXXV). Thisfunctional group manipulation gives various permutations in the sequence(VII) to (XXXIV) to (XXXV) as is apparent to one skilled in the art.When the appropriately R_(C)—N protected compound (XXXV) is reacted withthe amide forming agent (IX), in acid form, under standard peptidecoupling conditions, for example, EDC/HOBt in methylene chloride or DMFor a previously activated acid, (R_(N)—)₂O gives the correspondingR_(N)-substituted R_(C)—N protected (XXXVI). Simple de-protection of theR_(N)-substituted R_(C)—N protected (XXXVI) then gives the desiredsubstituted amine (X). Thus when the R_(N)-substituted R_(C)—N protected(XXXVI) is protected with BOC, treatment with hydrochloric acid (4N) indioxane or the other reagents discussed above gives the substitutedamine (X). When the R_(N)-substituted R_(C)—N protected (XXXVI) isprotected with CBZ, treatment with hydrogen from 10-50 psi in alcoholicsolvents, such as methanol with a catalytic amount of palladium oncarbon will give, after work-up, the desired substituted amine (X).Similarly when the R_(N-substituted) R_(C)—N protected (XXXVI) isprotected with FMOC, treatment with a secondary amine, preferably eitherpiperidine (10%) or diethylamine (10%) in an inert solvent such as, forexample, methylene chloride will give after work up the desiredsubstituted amine (X).

[1379] CHART J discloses a process to prepare compounds where the phenylring of the R_(N) substituent of —CO-phenyl-CO— is substituted with asulfonamide group in the 5-position. The process starts with the haloamide ester (XXI, CHART E) which is reacted with sodium nitrite, sulfurdioxide, copper chloride (II) and acetic acid by the method disclosed inJ. Med. Chem., 42, 3797 (1999) to prepare the sulfonyl chloride(XXXVII). The sulfonyl chloide (XXXVII) is then reacted with AMINE, asdefined above, by methods known to those skilled in the art to producethe corresponding sulfonamide (XXXVIII). Last the sulfonamide (XXXVIII)is transformed to the corresponding sulfonamide acid (XXMX) by methodsknown to those skilled in the art such as using lithium hydroxide,sodium hydroxide, potassium hydroxide, barium hydroxide, or otherhydrolysis methods known to those skilled in the art.

[1380] CHART K discloses how to prepare the R_(N) substituents whereR_(N) is R_(N-1)—X_(N)—, where X_(N) is —CO— and R_(N-1) is R_(N-aryl)where R_(N-aryl) is phenyl substituted with one alkyl group and one—CO—NR_(N-2)R_(N-3) or —CO—R_(N-4). See the discussion above for CHART Eregarding the amine, H-NR_(Nalpha)R_(Nbeta) (AMINE), used to form theamide R_(N) substituents. The process starts with the halo amide ester(XXI) which is then reacted with an alkyl boronic acid having thedesired alkyl group in the presence of a palladium catalyst such asPd(PPh₃)Cl₂ using the general method described in J. Med. Chem., 4288(2000). The alkyl boronic acids are commercially available or can beprepared by the process described in J. Am. Chem. Soc., 60, 105 (1938).It is preferred that R_(N-b) is bromo. This step produces the alkylester (XL) which is then hydrolyzed by means known to those skilled inthe art to produce the desired alkyl acid (XLI).

[1381] CHART L discloses a process to prepare the amide forming agent(IX-XLVII) where the R_(N) substituent is R_(N-1)—X_(N)—, where thelinker, —X_(N)— is —CO—, where R_(N-1) is R_(N-aryl) and whereR_(N-aryl) is phenyl (-phenyl) substituted with groups:

[1382] C₁-C₆ alkyl, optionally substituted with one, two or threesubstituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl,—Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) whereR_(1-a) and R_(1-b) are as defined above, and -N(—H and C₁-C₃alkyl)—CO—R_(N-5). This specific amide forming agent, (IX-XLVII) isprepared by starting with the phenyl nitro compoud (XLII) which isreduced to the corresponding phenyl nitro hydroxy compound (XLIII) usingborane-methyl sulfide or borane in THF. The phenyl nitro hydroxycompound (XLIII) is reduced to the corresponding phenyl amino hydroxycompound (XLIV) using hydrogen and palladium catalyst as is known tothose skilled in the art. The phenyl amino hydroxy compound (XLIV) isreacted with an aldehyde in the presence of a reducing agent such assodium cyanoborohydride or sodium triacetoxyborohydride to give thephenyl substituted amino hydroxy compound (XLV). The phenyl substitutedamino hydroxy compound (XLV) is acylated with an acid chloride or acidanhydride by methods known to those skilled in the art to give thephenyl disubstituted amino hydroxy compound (XLVI). The phenyldisubstituted amino hydroxy compound (XLVI) is hydrolyzed using analkali hydroxide, followed by acidification, to give the amide formingagent (IX-XLVII). The amide forming agent (XLVII) is then coupled withamine (VIII) using methods known to those skilled in the art and methodspreviously discussed, such as with diethyl cyanophosphonate, to give thesubstituted amine (X). Further treatment of the substituted amine (X)with diethyl cyanophosphonate gives the substituted amine where thehydroxyalkyl substitutent on the phenyl ring has a phosphatesubstitutent.

[1383] CHART M discloses a process to prepare amide forming agents(IX-L) where the R_(N) substituent is R_(N-1)—X_(N)—, where the linker,—X_(N)— is —CO—, where R_(N-1) is R_(N-aryl) and where R_(N-aryl) isphenyl (-phenyl) substituted with two groups. The first substituent atwhat is usually identified as position “5-” can be either:

[1384] —R_(N-aryl) or

[1385] —R_(N-heteroaryl). The second substituent at what is usuallyidentified as postion “3-” can be either:

[1386] —CO—NR_(N-2)R_(N-3) or

[1387] —CO—R_(N-4). R_(Nalpha) and R_(Nbeta) include both the non-cyclicamides,—CO—NR_(N-2)R_(N-3) and the cyclic amides-CO—R_(N-4) whereR_(N-2), R_(N-3) and R_(N-4) are as defined in the claims. The processstarts with the trisubstituted phenyl compound (XLVIII) where R_(N-d) is—Cl, —Br, —I or —O-triflate. Treatment with an aryl or heteroarylboronic acid or heteroaryl or aryl boronic acid ester such as (aryl orheteroaryl)-B(OH)₂ or (aryl or heteroaryl)-B(OR^(a))(OR^(b)) (whereR^(a) and R^(b) are lower alkyl, ie. C₁-C₆, or taken together, R^(a) andR^(b) are lower alkylene, ie. C₂-C₁₂) in the presence of a metalcatalyst with or without a base in an inert solvent yields (XLIX). Metalcatalysts in these transformations include, but are not limited to,salts or phosphine complexes of Cu, Pd, or Ni (eg. Cu(OAc)₂,PdCl₂(PPh₃)₂, NiCl₂(PPh₃)₂). Bases may include, but are not limited to,alkaline earth metal carbonates, alkaline earth metal bicarbonates,alkaline earth metal hydroxides, alkali metal carbonates, alkali metalbicarbonates, alkali metal hydroxides, alkali metal hydrides (preferablysodium hydride), alkali metal alkoxides (preferably sodium methoxide orsodium ethoxide), alkaline earth metal hydrides, alkali metaldialkylamides (preferably lithium diisopropylamide), alkali metalbis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide),trialkyl amines (preferably diisopropylethylamine or triethylamine) oraromatic amines (preferably pyridine). Inert solvents may include, butare not limited to, acetonitrile, dialkyl ethers (preferably diethylether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane),N,N-dialkylacetamides (preferably dimethylacetamide),N,N-dialkylformamides (preferably dimethylformamide), dialkylsulfoxides(preferably dimethylsulfoxide), aromatic hydrocarbons (preferablybenzene or toluene) or haloalkanes (preferably methylene chloride).Preferred reaction temperatures range from room temperature up to theboiling point of the solvent employed. The reactions may be run inconventional glassware or in one of many commercially available parallelsynthesizer units. Non-commercially available boronic acids or boronicacid esters may be obtained from the corresponding optionallysubstituted aryl halide as described in Tetrahedron, 50, 979-988 (1994).Intermediate (XLIX) is then hydrolyzed using alkali metal hydroxide, forexample lithium, sodium or potassium hydroxide, followed byacidification, to give aryl or heteroaryl coupled acids (IX-L).Alternatively, as described in Tetrahedron, 50, 979-988 (1994), one mayconvert the R_(N-d) to the corresponding boronic acid or boronic acidester (OH)₂B— or (OR^(a))(OR^(b))B— and obtain the same products setforth above by treating with a suitable aryl or heteroaryl halide ortriflate.

[1388] CHART N discloses a process to prepare amide forming agents(IX-LII) where the R_(N) substituent is R_(N1)—X_(N)— where the linker,—X_(N)— is —CO—, where R_(N-1) is R_(N-aryl) and where R_(N-aryl) isphenyl (-phenyl) substituted with two groups. The first substitutent atwhat is usually identified as postion “5-” is —C≡C—R. The secondsubstituent at what is usually identified as postion “3-” can be either—CO—NR_(N-2)R_(N-3) or —CO—R_(N-4). The halo ester (XXI) is treated witha mixture of PdCl₂(Pphenyl₃)₂ and trimethylsilyl acetylene, usingmethods known to those skilled in the art, to give acetylene ester (LI).Acetylene ester (LI) is then hydrolyzed using alkali metal hydroxide,followed by acidification, to give acetylene acid (IX-LII).

[1389] CHARTs O and O′ disclose processes to prepare amide formingagents (IX-LX) and (IX-LXIII) with an extended methylene group where theR_(N) substituent is R_(N-1)—X_(N)— where the linker, —X_(N)— is —CO—,where R_(N-1) is R_(N-aryl) and where R_(N-aryl) is phenyl (-phenyl)substituted with two groups. The substituent at what is usuallyidentified as postion “3-” can be either —CO—NR_(N-2)R_(N-3) or—CO—R_(N-4). In the process of CHART O, the substituent at the5-position is —CH₂CO—NH₂ and in the process of CHART O′, the substituentat the 5-position is —CH₂C—N. The starting diester acid (LIII) isreduced with borane in solvents such as THF to give the correspondingdiester alcohol (LIV). The diester alcohol (LIV) is converted to thecorresponding diester bromo compound (LV) using a brominating agent suchas PBr₃, CBr₄, or other halogenating agent such as are known to thoseskilled in the art. The bromine of the diester bromo compound (LV) isthen displaced with cyanide to give the corresponding nitrile (LVI). InCHART O′, the nitrile (LVI) is then hydrolyzed to the correspondingcyano ester (LXI). The cyano ester (LXI) is then coupled withH-NR_(Nα)R_(Nβ) (AMINE), as previously described using methods known tothose skilled in the art to give the corresponding cyano amide (LXII).The cyano amide (LXII) is then hydrolyzed to the corresponding cyanoacid (IX-LXIII) which is in turn coupled with amine (VIII) to give thesubstituted amine (X). When the substitutent on the extended methylgroup is —CO—NH₂, the process of CHART O is used. There the nitrile(LVI) is converted to the corresponding diester amine (LVII) by methodsknown to those skilled in the art. The next steps are the same as forCHART O′ where the diester amide (LVII) is hydrolyzed to thecorresponding ester amine (LVIII) which is then converted to thecorresponding diamide ester (LIX) which is hydrolyzed to thecorresponding diamide acid (IX-LX). The diamide acid (IX-XL) is thencoupled with the appropriate amine (VIII) to produce the desiredsubstituted amide (X).

[1390] CHART P discloses a process to prepare amide forming agents(IX-LXVII) with an extended hydroxymethylene group where the R_(N)substituent is R_(N-1)—X_(N)— where the linker, —X_(N)— is —CO—, wherethe R_(N-1) is R_(N-aryl), where R_(N-aryl) is phenyl (-phenyl)substituted with two groups. The substituent at what is usuallyidentified as position “3-” can be either —CO—NR_(N-2)R_(N-3) or—CO—R_(N-4). The process begins with a halo amide (LXIV), preferablyiodo, which is converted to the corresponding aldehyde (LXV) and then tothe corresponding alcohol (LXVI) by the method described in Synth.Commun. 28, 4270 (1998), optionally with variations known to thoseskilled in the art. Hydrolysis of the alcohol (LXVI) using alkalihydroxides, followed by acidification, gives the desired hydroxy acid(IX-LXVII). The hydroxy acid (IX-LXVII) is then coupled with theappropriate amine (VIII) to give the desired substituted amine (X).

[1391] CHART Q discloses a process to prepare amide forming agents(IX-LXXII) with an alkyl group or a halogen atom or an amino group atthe 5-position where the R_(N) substituent is R_(N-1)—X_(N)— where thelinker, —X_(N)— is —CO—, where the R_(N-1) is R_(N-aryl), whereR_(N-aryl) is phenyl (-phenyl) substituted with two groups. Thesubstituent at what is usually identified as position “3-” can be either—CO—NR_(N-2)R_(N-3) or —CO—R_(N-4). The process begins with anappropriately 5-substituted diacid (LXVIII) which is esterified bymethods known to those skilled in the art to give the correspondingdiester (LXIX). The diester (LXIX) is then hydrolyzed using alkalihydroxides, followed by acidification, to give the correspondingmonoacid (LXX). Alternatively, the monoacid (LXX) can be produceddirectly from the diacid (LXVIII) by known methods. The monoacid (LXX)is then coupled with H-NR_(Nalpha)R_(Nbeta) (AMINE) to give thecorresponding amide ester (LXXI). The amide ester (LXXI) is thenhydrolyzed using alkali hydroxides, followed by acidification, to givethe corresponding acid amide (IX-LXXII).

[1392] CHART R discloses a general process to prepare the amide formingagents (IX-LXXVII) which, for example, have an alkyl group at what isknown as the 5-position and a ketone at the 3-position. These acids(IX-LXXVII) are formed by starting with the acid (LXXIII) which isconverted to the corresponding acid halide (LXXIV) using methods knownto those skilled in the art. The acid halide (LXXIV) is preferrably theacid chloride. The acid halide (LXXIV) in the presence of copper (I)bromide and tetrahydrofuran and at temperatures ranging from −78 degreesC. to 0 degrees C. is treated with a Grignard reagent (aryl-Mg-X, oralkyl-Mg—X, where X is —Cl or —Br) to give the ketone esters (LXXVI andLXXVI′). Many Grignard reagents are available for purchase; others areprepared by methods known to those skilled in the art. An alternativemethod for preparing the ketone esters (LXXVI, LXXVI′) is to prepare theWeinreb amide (LXXV), either from the acid (LXXIII) directly or by wayof acid halide (LXXIV) followed by treatment withN,O-dimethylhydroxylamine to give Weinreb amide (LXXV) and then treatingthe Weinreb amide (LXXV) with a Grignard reagent, by methods known tothose skilled in the art. The ketone esters (LXXVI, LXXVI′) are thenhydrolyzed using alkali hydroxides, followed by acidification, to givethe ketone acids (LXXVII, LXXVII′).

[1393] CHART S discloses various methods to modify the R_(N) portion ofthe substituted amine (X) where the phenyl ring of the R_(N) moiety isfurther substituted in the 3-position with various groups such as aryland heteroaryl. These compounds are prepared by methods known to thoseskilled in the art. The process chemistry of each reaction is known tothose skilled in the art. What is novel here is the order of eachprocess step and/or the specific reactants used. One skilled in the artknowing the desired product would know at least one method to preparethe desired product by using known starting materials. Hence, thefollowing discussion is not necessary but is set forth to further aidthose interested in preparing the compounds of the invention.

[1394] CHART S sets forth a general method used in the present inventionto prepare the substitued amines (X) whereR_(N)═R_(N)-aryl-R_(N)-aryl-X_(N) or R_(N-heteroaryl)—R_(N-aryl)-X_(N).Treatment of the (S,R)-amine (VIII) with amide forming agents (IX)according to the methods set forth above where for CHART S, R_(N-1) isBr—R_(N-aryl) generates the corresponding (S,R)-substituted amine (X)where R_(N) is Br—N_(R-aryl)—X_(N). Further treatment with an arylboronic acid or aryl boronic acid ester such as (aryl orheteroaryl)-B(OH)₂ or (aryl or heteroaryl)-B(OR^(a))(OR^(b)) (whereR^(a) and R^(b) are lower alkyl, ie. C₁-C₆, or taken together, R^(a) andR^(b) are lower alkylene, ie. C₂-C₁₂) in the presence of a metalcatalyst with or without a base in an inert solvent yields the(S,R)-substituted amine (X) where R_(N) is N_(R-aryl)-N_(R-aryl)—X_(N)or R_(N-heteroaryl)—R_(N-aryl)—X_(N). Metal catalysts in thesetransformations include, but are not limited to, salts or phosphinecomplexes of Cu, Pd, or Ni (eg. Cu(OAc)₂, PdCl₂(PPh₃)₂, NiCl₂(PPh₃)₂).Bases may include, but are not limited to, alkaline earth metalcarbonates, alkaline earth metal bicarbonates, alkaline earth metalhydroxides, alkali metal carbonates, alkali metal bicarbonates, alkalimetal hydroxides, alkali metal hydrides (preferably sodium hydride),alkali metal alkoxides (preferably sodium methoxide or sodium ethoxide),alkaline earth metal hydrides, alkali metal dialkylamides (preferablylithium diisopropylamide), alkali metal bis(trialkylsilyl)amides(preferably sodium bis(trimethylsilyl)amide), trialkyl amines(preferably diisopropylethylamine or triethylamine) or aromatic amines(preferably pyridine). Inert solvents may include, but are not limitedto, acetonitrile, dialkyl ethers (preferably diethyl ether), cyclicethers (preferably tetrahydrofuran or 1,4-dioxane),N,N-dialkylacetamides (preferably dimethylacetamide),N,N-dialkylformamides (preferably dimethylformamide), dialkylsulfoxides(preferably dimethylsulfoxide), aromatic hydrocarbons (preferablybenzene or toluene) or haloaalkanes (preferably methylene chloride).Preferred reaction temperatures range from room temperature up to theboiling point of the solvent employed. The reactions may be run inconventional glassware or in one of many commercially available parallelsynthesizer units. Non-commercially available boronic acids or boronicacid esters may be obtained from the corresponding optionallysubstituted aryl halide as described in Tetrahedron, 50, 979-988 (1994).

[1395] Where the above chemistry is incompatible with otherfunctionality present in the (S,R)-substituted amine (X) where R_(N) isBr—N_(R-aryl)—X_(N), then one skilled in the art will readily understandthat an alternative sequence of coupling steps is required. For example,treatment of an appropriately substituted amide forming agent (IX)R_(N-1) —X_(N)—OH where R_(N-1) is Br—R_(N-aryl) with a boronic acid orboronic acid ester under the conditions described above will afford theappropriately substituted amide forming agent (IX) where R_(N-1) isN_(R-aryl)—N_(R-aryl) or R_(N-heteroaryl)—R_(N-aryl). When the amideforming agent (IX) where R_(N-1) is N_(R-aryl)—N_(R-aryl) orR_(N-heteroaryl)—R_(N-aryl) is treated with the (S,R)-amine (VIII), onethen obtains the same substituted amines (X) set forth in CHART S.

[1396] The above examples for CHART S are not meant to limit the scopeof the chemistry. In addition to bromine, a suitable group may includeiodine or triflate. Alternatively, as described in Tetrahedron, 50,979-988 (1994), one may convert the Br—R_(N-aryl) to the correspondingboronic acid or boronic acid ester (OH)₂B—R_(N-aryl) or(OR^(a))(OR^(b))B—R_(N-aryl) and obtain the same products set forthabove by treating with a suitable aryl or heteroaryl halide or triflate.Additionally, each —R_(N-aryl) and —R_(N-heteroaryl) are interchangeableat each occurrence in the chemistry described above.

[1397] CHART T discloses a process to prepare amide forming agents(IX-LXXIX) where the R_(N) substituent is R_(N-1)—X_(N)—, where thelinker, —X_(N)— is —CO—, where RN—, is R_(N-aryl) and where R_(N-aryl)is phenyl substituted with —CO—NR_(Nalpha)R_(Nbeta) (AMINE) and with anamide of the formulas:

—(CH₂)₀₋₄—N(—H and R_(N-5))—CO—R_(N-2)

—(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2).

[1398] The process begins with the amide aniline (XXXI) which is reactedwith the corresponding acid halide or sulfonyl halide, or acid anhydrideor sulfonyl anhydride to produce the corresponding amide ester(LXXVIII). Suitable solvents include TBF or dichloromethane attemperatures ranging from −78 degrees to 100 degrees C. The amide ester(LXXVIII) is then hydrolyzed to the corresponding amide acid (IX-LXXIX)by methods known to those skilled in the art. When the amide formingagent (IX-LXXIX) is reacted with the appropriate amine (VIII), thedesired substituted amine (X) is obtained.

[1399] CHART U discloses a general method for preparing variousC-terminal amines (VI) as represented by the preparation of C-terminalamine (LXXXIV). Methods to prepare amines of this type are wellunderstood using methods known to those skilled in the art, or one mayconsult the references: 1) JACS, 1970, 92, 3700, and 2) U.S. Pat. No.4,351,842.

[1400] CHART V further discloses general methods for preparing variousC-terminal amines (VI) as represented by the preparation of C-terminalamines (LXXXIX). Multiple examples of the heterocyclic carboxylic acidsor acid chlorides are commercially available. Optionally, the carboxylicacid (LXXXV) may be converted to the acid chloride (LXXXVI) withreagents such as, but not limited to, thionyl chloride. Displacementwith ammonia generates the common intermediate amides (LXXXVII) whichare readily reduced to amines (VI-LXXXIX) using a variety of methodsdetailed previously. Alternatively, other heteroaryls are commeciallyavailable as the methyl halide (LXXXVIII) which are treated with ammoniato yield the title C-terminal amines (VI-LXXXVIII).

[1401] CHART W discloses general methods for preparing thiazolylcontaining C-terminal amines as represented by the preparation ofC-terminal amines (LXXXXI). The synthesis of the thiazoles is outlinedin CHART W; these procedures are amply taught in the literature and aremodified from the procedures outlined in: Mashraqui, S H; Keehn, P M. J.Am. Chem. Soc. 1982, 104,44614465. The synthesis of substituted5-aminomethylthiazoles (XCI) was achieved from 5-hydroxymethylthiazole(XC) by the procedure described in: Alterman et al. J. Med. Chem. 1998,41, 3782-3792. All other thiazole analogs were transformed to thehydroxymethyl derivative using CHART W, and converted to the aminomethylderivative by the Alterman procedure without notable changes.

[1402] CHART X discloses general methods for preparing isoxazolylcontaining C-terminal amines as represented by the preparation ofC-terminal amines (XCII). The synthesis of isoxazole derivatives wasmodified from the procedure in: Felman, S W et al. J. Med. Chem. 1992,35, 1183-1190 and is readily understood by those skilled in the artmaking non-notable changes to achieve the title compounds. Thesubstituted hydroxylamine precursors were synthesized using theprocedure taught by Bousquet, E W. Org. Synth. Coll. Vol II, 313-315.Commercially available propargylamine may be protected using any numberof methods known in the art (see: Greene, T W; Wuts, P G M. ProtectiveGroups in Organic Synthesis, 3^(rd) Ed. New York: John Wiley, 1999.Chapter 7.), prefered is a BOC protecting group. Substituted propargylamines may be obtained by a number of methods commonly known in the art.

[1403] CHART Y discloses a general route to prepare hydroxyethylamineswhere one carbon atom of the peptide backbone, along with R₂ and R₃ forma ring. It is understood that the present invention also allows for aheteroatom to be incorporated into the ring. In summary, the synthesisof compounds where R₂ and R₃ may form a ring proceeds from a suitablyprotected amino acid aldehyde and cycloalkyllithium species, both ofwhich are commercially available or where known procedures for makingsuch compounds are known in the art. The general procedure involved isalso precedent in the literature, for example, see Klumpp, et al., J.Am. Chem. Soc., 1979, 101, 7065, and it is intended that makingnon-critical variations, one may obtain the title compounds provided forby CHART Y. Treatment of a suitably protected amino acid aldehyde andcycloalkyllithium species affords alcohol (XCIII). These reactions arecarried out in an inert solvent such as, for example, tetrahydrofuran ordiethyl ether. Optimally the reactions are conducted at lowtemperatures, for example below 0 degrees C. Carbonylation via theKlumpp procedure yields the acid (XCIV) which when exposed to Curtius,or related procedures well known to those skilled in the art, generatesthe primary amine (XCV). The primary amines (XCV) may be cappedC-terminally via the conditions set forth in CHART C & D followed bynitrogen deprotection and capping N-terminally via the conditions setforth in CHART A.

[1404] The compounds of the invention may contain geometric or opticalisomers as well as tautomers. Thus, the invention includes all tautomersand pure geometric isomers, such as the E and Z geometric isomers, aswell as mixtures thereof. Futhermore, the invention includes pureenantiomers and diasteriomers as well as mixtures thereof, includingracemic mixtures. The individual geometric isomers, enantiomers, ordiasteriomers may be prepared or isolated by methods known in the art.

[1405] Compounds of the invention with the stereochemistry designated informula X may be included in mixtures, including racemic mixtures, withother enantiomers, diasteriomers, geometric isomers or tautomers.Compounds of the invention with the stereochemistry designated informula X are typically present in these mixtures in excess of 50percent. Preferably, compounds of the invention with the stereochemistrydesignated in formula X are present in these mixtures in excess of 80percent. Most preferably, compounds of the invention with thestereochemistry designated in formula X are present in these mixtures inexcess of 90 percent.

[1406] The (S,R)-substituted amines (X) and the substituted amine withR_(N) cyclized (X′) are amines and as such form salts when reacted withacids. Pharmaceutically acceptable salts are preferred over thecorresponding (S,R)-substituted amines (X) and and the substitutedamines with R_(N) cyclized (X′) since they produce compounds which aremore water soluble, stable and/or more crystalline. Pharmaceuticallyacceptable salts are any salt which retains the activity of the parentcompound and does not impart any deleterious or undesirable effect onthe subject to whom it is administered and in the context in which it isadministered. Pharmaceutically acceptable salts include salts of bothinorganic and organic acids. The preferred pharmaceutically acceptablesalts include salts of the following acids acetic, aspartic,benzenesulfonic, benzoic, bicarbonic, bisulfuiric, bitartaric, butyric,calcium edetate, camsylic, carbonic, chlorobenzoic, citric, edetic,edisylic, estolic, esyl, esylic, formic, fumaric, gluceptic, gluconic,glutamic, glycollylarsanilic, hexamic, hexylresorcinoic, hydrabamic,hydrobromic, hydrochloric, hydroiodic, hydroxynaphthoic, isethionic,lactic, lactobionic, maleic, malic, malonic, mandelic, methanesulfonic,methylnitric, methylsulfuric, mucic, muconic, napsylic, nitric, oxalic,p-nitromethanesulfonic, pamoic, pantothenic, phosphoric, monohydrogenphosphoric, dihydrogen phosphoric, phthalic, polygalactouronic,propionic, salicylic, stearic, succinic, succinic, sulfamic, sulfanilic,sulfonic, sulfuric, tannic, tartaric, teoclic and toluenesulfonic. Forother acceptable salts, see Int. J. Pharm., 33, 201-217 (1986) andJ.Pharm.Sci., 66(1), 1, (1977).

[1407] The present invention provides compounds, compositions, kits, andmethods for inhibiting beta-secretase enzyme activity and A beta peptideproduction. Inhibition of beta-secretase enzyme activity halts orreduces the production of A beta from APP and reduces or eliminates theformation of beta-amyloid deposits in the brain.

METHODS OF THE INVENTION

[1408] The compounds of the invention, and pharmaceutically acceptablesalts thereof, are useful for treating humans or animals suffering froma condition characterized by a pathological form of beta-amyloidpeptide, such as beta-amyloid plaques, and for helping to prevent ordelay the onset of such a condition. For example, the compounds areuseful for treating Alzheimer's disease, for helping prevent or delaythe onset of Alzheimer's disease, for treating patients with MCI (mildcognitive impairment) and preventing or delaying the onset ofAlzheimer's disease in those who would progress from MCI to AD, fortreating Down's syndrome, for treating humans who have HereditaryCerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treatingcerebral amyloid angiopathy and preventing its potential consequences,i.e. single and recurrent lobal hemorrhages, for treating otherdegenerative dementias, including dementias of mixed vascular anddegenerative origin, dementia associated with Parkinson's disease,dementia associated with progressive supranuclear palsy, dementiaassociated with cortical basal degeneration, and diffuse Lewy body typeAlzheimer's disease. The compounds and compositions of the invention areparticularly useful for treating or preventing Alzheimer's disease. Whentreating or preventing these diseases, the compounds of the inventioncan either be used individually or in combination, as is best for thepatient.

[1409] As used herein, the term “treating” means that the compounds ofthe invention can be used in humans with at least a tentative diagnosisof disease. The compounds of the invention will delay or slow theprogression of the disease thereby giving the individual a more usefullife span.

[1410] The term “preventing” means that the compounds of the presentinvention are useful when administered to a patient who has not beendiagnosed as possibly having the disease at the time of administration,but who would normally be expected to develop the disease or be atincreased risk for the disease. The compounds of the invention will slowthe development of disease symptoms, delay the onset of the disease, orprevent the individual from developing the disease at all. Preventingalso includes administration of the compounds of the invention to thoseindividuals thought to be predisposed to the disease due to age,familial history, genetic or chromosomal abnormalities, and/or due tothe presence of one or more biological markers for the disease, such asa known genetic mutation of APP or APP cleavage products in braintissues or fluids.

[1411] In treating or preventing the above diseases, the compounds ofthe invention are administered in a therapeutically effective amount.The therapeutically effective amount will vary depending on theparticular compound used and the route of administration, as is known tothose skilled in the art.

[1412] In treating a patient displaying any of the diagnosed aboveconditions a physician may administer a compound of the inventionimmediately and continue administration indefinitely, as needed. Intreating patients who are not diagnosed as having Alzheimer's disease,but who are believed to be at substantial risk for Alzheimer's disease,the physician should preferably start treatment when the patient firstexperiences early pre-Alzheimer's symptoms such as, memory or cognitiveproblems associated with aging. In addition, there are some patients whomay be determined to be at risk for developing Alzheimer's through thedetection of a genetic marker such as APOE4 or other biologicalindicators that are predictive for Alzheimer's disease. In thesesituations, even though the patient does not have symptoms of thedisease, administration of the compounds of the invention may be startedbefore symptoms appear, and treatment may be continued indefinitely toprevent or delay the outset of the disease.

[1413] Dosage Forms and Amounts

[1414] The compounds of the invention can be administered orally,parentemally, (IV, IM, depo-IM, SQ, and depo SQ), sublingually,intranasally (inhalation), intrathecally, topically, or rectally. Dosageforms known to those of skill in the art are suitable for delivery ofthe compounds of the invention.

[1415] Compositions are provided that contain therapeutically effectiveamounts of the compounds of the invention. The compounds are preferablyformulated into suitable pharmaceutical preparations such as tablets,capsules, or elixirs for oral administration or in sterile solutions orsuspensions for parentemal administration. Typically the compoundsdescribed above are formulated into pharmaceutical compositions usingtechniques and procedures well known in the art.

[1416] About 1 to 500 mg of a compound or mixture of compounds of theinvention or a physiologically acceptable salt or ester is compoundedwith a physiologically acceptable vehicle, carrier, excipient, binder,preservative, stabilizer, flavor, etc., in a unit dosage form as calledfor by accepted pharmaceutical practice. The amount of active substancein those compositions or preparations is such that a suitable dosage inthe range indicated is obtained. The compositions are preferablyformulated in a unit dosage form, each dosage containing from about 2 toabout 100 mg, more preferably about 10 to about 30 mg of the activeingredient. The term “unit dosage from” refers to physically discreteunits suitable as unitary dosages for human subjects and other mammals,each unit containing a predetermined quantity of active materialcalculated to produce the desired therapeutic effect, in associationwith a suitable pharmaceutical excipient.

[1417] To prepare compositions, one or more compounds of the inventionare mixed with a suitable pharmaceutically acceptable carrier. Uponmixing or addition of the compound(s), the resulting mixture may be asolution, suspension, emulsion, or the like. Liposomal suspensions mayalso be suitable as pharmaceutically acceptable carriers. These may beprepared according to methods known to those skilled in the art. Theform of the resulting mixture depends upon a number of factors,including the intended mode of administration and the solubility of thecompound in the selected carrier or vehicle. The effective concentrationis sufficient for lessening or ameliorating at least one symptom of thedisease, disorder, or condition treated and may be empiricallydetermined.

[1418] Pharmaceutical carriers or vehicles suitable for administrationof the compounds provided herein include any such carriers known tothose skilled in the art to be suitable for the particular mode ofadministration. In addition, the active materials can also be mixed withother active materials that do not impair the desired action, or withmaterials that supplement the desired action, or have another action.The compounds may be formulated as the sole pharmaceutically activeingredient in the composition or may be combined with other activeingredients.

[1419] Where the compounds exhibit insufficient solubility, methods forsolubilizing may be used. Such methods are known and include, but arenot limited to, using cosolvents such as dimethylsulfoxide (DMSO), usingsurfactants such as Tween(D, and dissolution in aqueous sodiumbicarbonate. Derivatives of the compounds, such as salts or prodrugs mayalso be used in formulating effective pharmaceutical compositions.

[1420] The concentration of the compound is effective for delivery of anamount upon administration that lessens or ameliorates at least onesymptom of the disorder for which the compound is administered.Typically, the compositions are formulated for single dosageadministration.

[1421] The compounds of the invention may be prepared with carriers thatprotect them against rapid elimination from the body, such astime-release formulations or coatings. Such carriers include controlledrelease formulations, such as, but not limited to, microencapsulateddelivery systems. The active compound is included in thepharmaceutically acceptable carrier in an amount sufficient to exert atherapeutically useful effect in the absence of undesirable side effectson the patient treated. The therapeutically effective concentration maybe determined empirically by testing the compounds in known in vitro andin vivo model systems for the treated disorder.

[1422] The compounds and compositions of the invention can be enclosedin multiple or single dose containers. The enclosed compounds andcompositions can be provided in kits, for example, including componentparts that can be assembled for use. For example, a compound inhibitorin lyophilized form and a suitable diluent may be provided as separatedcomponents for combination prior to use. A kit may include a compoundinhibitor and a second therapeutic agent for co-administration. Theinhibitor and second therapeutic agent may be provided as separatecomponent parts. A kit may include a plurality of containers, eachcontainer holding one or more unit dose of the compound of theinvention. The containers are preferably adapted for the desired mode ofadministration, including, but not limited to tablets, gel capsules,sustained-release capsules, and the like for oral administration; depotproducts, pre-filled syringes, ampules, vials, and the like forparenternal administration; and patches, medipads, creams, and the likefor topical administration.

[1423] The concentration of active compound in the drug composition willdepend on absorption, inactivation, and excretion rates of the activecompound, the dosage schedule, and amount administered as well as otherfactors known to those of skill in the art.

[1424] The active ingredient may be administered at once, or may bedivided into a number of smaller doses to be administered at intervalsof time. It is understood that the precise dosage and duration oftreatment is a function of the disease being treated and may bedetermined empirically using known testing protocols or by extrapolationfrom in vivo or in vitro test data. It is to be noted thatconcentrations and dosage values may also vary with the severity of thecondition to be alleviated. It is to be further understood that for anyparticular subject, specific dosage regimens should be adjusted overtime according to the individual need and the professional judgment ofthe person administering or supervising the administration of thecompositions, and that the concentration ranges set forth herein areexemplary only and are not intended to limit the scope or practice ofthe claimed compositions.

[1425] If oral administration is desired, the compound should beprovided in a composition that protects it from the acidic environmentof the stomach. For example, the composition can be formulated in anenteric coating that maintains its integrity in the stomach and releasesthe active compound in the intestine. The composition may also beformulated in combination with an antacid or other such ingredient.

[1426] Oral compositions will generally include an inert diluent or anedible carrier and may be compressed into tablets or enclosed in gelatincapsules. For the purpose of oral therapeutic administration, the activecompound or compounds can be incorporated with excipients and used inthe form of tablets, capsules, or troches. Pharmaceutically compatiblebinding agents and adjuvant materials can be included as part of thecomposition.

[1427] The tablets, pills, capsules, troches, and the like can containany of the following ingredients or compounds of a similar nature: abinder such as, but not limited to, gum tragacanth, acacia, corn starch,or gelatin; an excipient such as microcrystalline cellulose, starch, orlactose; a disintegrating agent such as, but not limited to, alginicacid and corn starch; a lubricant such as, but not limited to, magnesiumstearate; a gildant, such as, but not limited to, colloidal silicondioxide; a sweetening agent such as sucrose or saccharin; and aflavoring agent such as peppermint, methyl salicylate, or fruitflavoring.

[1428] When the dosage unit form is a capsule, it can contain, inaddition to material of the above type, a liquid carrier such as a fattyoil. In addition, dosage unit forms can contain various other materials,which modify the physical form of the dosage unit, for example, coatingsof sugar and other enteric agents. The compounds can also beadministered as a component of an elixir, suspension, syrup, wafer,chewing gum or the like. A syrup may contain, in addition to the activecompounds, sucrose as a sweetening agent and certain preservatives, dyesand colorings, and flavors.

[1429] The active materials can also be mixed with other activematerials that do not impair the desired action, or with materials thatsupplement the desired action.

[1430] Solutions or suspensions used for parenternal, intradermal,subcutaneous, or topical application can include any of the followingcomponents: a sterile diluent such as water for injection, salinesolution, fixed oil, a naturally occurring vegetable oil such as sesameoil, coconut oil, peanut oil, cottonseed oil, and the like, or asynthetic fatty vehicle such as ethyl oleate, and the like, polyethyleneglycol, glycerine, propylene glycol, or other synthetic solvent;antimicrobial agents such as benzyl alcohol and methyl parabens;antioxidants such as ascorbic acid and sodium bisulfite; chelatingagents such as ethylenediaminetetraacetic acid (EDTA); buffers such asacetates, citrates, and phosphates; and agents for the adjustment oftonicity such as sodium chloride and dextrose. Parenternal preparationscan be enclosed in ampoules, disposable syringes, or multiple dose vialsmade of glass, plastic, or other suitable material. Buffers,preservatives, antioxidants, and the like can be incorporated asrequired.

[1431] Where administered intravenously, suitable carriers includephysiological saline, phosphate buffered saline (PBS), and solutionscontaining thickening and solubilizing agents such as glucose,polyethylene glycol, polypropyleneglycol, and mixtures thereof.Liposomal suspensions including tissue-targeted liposomes may also besuitable as pharmaceutically acceptable carriers. These may be preparedaccording to methods known for example, as described in U.S. Pat. No.4,522,811.

[1432] The active compounds may be prepared with carriers that protectthe compound against rapid elimination from the body, such astime-release formulations or coatings. Such carriers include controlledrelease formulations, such as, but not limited to, implants andmicroencapsulated delivery systems, and biodegradable, biocompatiblepolymers such as collagen, ethylene vinyl acetate, polyanhydrides,polyglycolic acid, polyorthoesters, polylactic acid, and the like.Methods for preparation of such formulations are known to those skilledin the art.

[1433] The compounds of the invention can be administered orally,parenternally (IV, IM, depo-IM, SQ, and depo-SQ), sublingually,intranasally (inhalation), intrathecally, topically, or rectally. Dosageforms known to those skilled in the art are suitable for delivery of thecompounds of the invention.

[1434] Compounds of the invention may be administered enterally orparenterally. When administered orally, compounds of the invention canbe administered in usual dosage forms for oral administration as is wellknown to those skilled in the art. These dosage forms include the usualsolid unit dosage forms of tablets and capsules as well as liquid dosageforms such as solutions, suspensions, and elixirs. When the solid dosageforms are used, it is preferred that they be of the sustained releasetype so that the compounds of the invention need to be administered onlyonce or twice daily.

[1435] The oral dosage forms are administered to the patient 1, 2, 3, or4 times daily. It is preferred that the compounds of the invention beadministered either three or fewer times, more preferably once or twicedaily. Hence, it is preferred that the compounds of the invention beadministered in oral dosage form. It is preferred that whatever oraldosage form is used, that it be designed so as to protect the compoundsof the invention from the acidic environment of the stomach. Entericcoated tablets are well known to those skilled in the art. In addition,capsules filled with small spheres each coated to protect from theacidic stomach, are also well known to those skilled in the art.

[1436] When administered orally, an administered amount therapeuticallyeffective to inhibit beta-secretase activity, to inhibit A betaproduction, to inhibit A beta deposition, or to treat or prevent AD isfrom about 0.1 mg/day to about 1,000 mg/day. It is preferred that theoral dosage is from about 1 mg/day to about 100 mg/day. It is morepreferred that the oral dosage is from about 5 mg/day to about 50mg/day. It is understood that while a patient may be started at onedose, that dose may be varied over time as the patient's conditionchanges.

[1437] Compounds of the invention may also be advantageously deliveredin a nano crystal dispersion formulation. Preparation of suchformulations is described, for example, in U.S. Pat. No. 5,145,684. Nanocrystalline dispersions of HIV protease inhibitors and their method ofuse are described in U.S. Pat. No. 6,045,829. The nano crystallineformulations typically afford greater bioavailability of drug compounds.

[1438] The compounds of the invention can be administered parenterally,for example, by IV, IM, depo-IM, SC, or depo-SC. When administeredparenterally, a therapeutically effective amount of about 0.5 to about100 mg/day, preferably from about 5 to about 50 mg daily should bedelivered. When a depot formulation is used for injection once a monthor once every two weeks, the dose should be about 0.5 mg/day to about 50mg/day, or a monthly dose of from about 15 mg to about 1,500 mg. In partbecause of the forgetfulness of the patients with Alzheimer's disease,it is preferred that the parenteral dosage form be a depo formulation.

[1439] The compounds of the invention can be administered sublingually.When given sublingually, the compounds of the invention should be givenone to four times daily in the amounts described above for IMadministration.

[1440] The compounds of the invention can be administered intranasally.When given by this route, the appropriate dosage forms are a nasal sprayor dry powder, as is known to those skilled in the art. The dosage ofthe compounds of the invention for intranasal administration is theamount described above for IM administration.

[1441] The compounds of the invention can be administered intrathecally.When given by this route the appropriate dosage form can be aparenternal dosage form as is known to those skilled in the art. Thedosage of the compounds of the invention for intrathecal administrationis the amount described above for IM administration.

[1442] The compounds of the invention can be administered topically.When given by this route, the appropriate dosage form is a cream,ointment, or patch. Because of the amount of the compounds of theinvention to be administered, the patch is preferred. When administeredtopically, the dosage is from about 0.5 mg/day to about 200 mg/day.Because the amount that can be delivered by a patch is limited, two ormore patches may be used. The number and size of the patch is notimportant, what is important is that a therapeutically effective amountof the compounds of the invention be delivered as is known to thoseskilled in the art. The compounds of the invention can be administeredrectally by suppository as is known to those skilled in the art. Whenadministered by suppository, the therapeutically effective amount isfrom about 0.5 mg to about 500 mg.

[1443] The compounds of the invention can be administered by implants asis known to those skilled in the art. When administering a compound ofthe invention by implant, the therapeutically effective amount is theamount described above for depot administration.

[1444] The invention here is the new compounds of the invention and newmethods of using the compounds of the invention. Given a particularcompound of the invention and a desired dosage form, one skilled in theart would know how to prepare and administer the appropriate dosageform.

[1445] The compounds of the invention are used in the same manner, bythe same routes of administration, using the same pharmaceutical dosageforms, and at the same dosing schedule as described above, forpreventing disease or treating patients with MCI (mild cognitiveimpairment) and preventing or delaying the onset of Alzheimer's diseasein those who would progress from MCI to AD, for treating or preventingDown's syndrome, for treating humans who have Hereditary CerebralHemorrhage with Amyloidosis of the Dutch-Type, for treating cerebralamyloid angiopathy and preventing its potential consequences, i.e.single and recurrent lobar hemorrhages, for treating other degenerativedementias, including dementias of mixed vascular and degenerativeorigin, dementia associated with Parkinson's disease, dementiaassociated with progressive supranuclear palsy, dementia associated withcortical basal degeneration, and diffuse Lewy body type of Alzheirner'sdisease.

[1446] The compounds of the invention can be used in combination, witheach other or with other therapeutic agents or approaches used to treator prevent the conditions listed above. Such agents or approachesinclude: acetylcholine esterase inhibitors such as tacrine(tetrahydroaminoacridine, marketed as COGNEX®), donepezil hydrochloride,(marketed as Aricept® and rivastigmine (marketed as Exelon®);gamma-secretase inhibitors; anti-inflammatory agents such ascyclooxygenase II inhibitors; anti-oxidants such as Vitamin E andginkolides; immunological approaches, such as, for example, immunizationwith A beta peptide or administration of anti-A beta peptide antibodies;statins; and direct or indirect neurotropic agents such asCerebrolysin®, AIT-082 (Emilieu, 2000, Arch. Neurol. 57:454), and otherneurotropic agents of the future.

[1447] It should be apparent to one skilled in the art that the exactdosage and frequency of administration will depend on the particularcompounds of the invention administered, the particular condition beingtreated, the severity of the condition being treated, the age, weight,general physical condition of the particular patient, and othermedication the individual may be taking as is well known toadministering physicians who are skilled in this art.

[1448] Inhibition of APP Cleavage

[1449] The compounds of the invention inhibit cleavage of APP betweenMet595 and Asp596 numbered for the APP695 isoform, or a mutant thereof,or at a corresponding site of a different isoform, such as APP751 orAPP770, or a mutant thereof (sometimes referred to as the “betasecretase site”). While not wishing to be bound by a particular theory,inhibition of beta-secretase activity is thought to inhibit productionof beta amyloid peptide (A beta). Inhibitory activity is demonstrated inone of a variety of inhibition assays, whereby cleavage of an APPsubstrate in the presence of a beta-secretase enzyme is analyzed in thepresence of the inhibitory compound, under conditions normallysufficient to result in cleavage at the beta-secretase cleavage site.Reduction of APP cleavage at the beta-secretase cleavage site comparedwith an untreated or inactive control is correlated with inhibitoryactivity. Assay systems that can be used to demonstrate efficacy of thecompound inhibitors of the invention are known. Representative assaysystems are described, for example, in U.S. Pat. No. 5,942,400,5,744,346, as well as in the Examples below.

[1450] The enzymatic activity of beta-secretase and the production of Abeta can be analyzed in vitro or in vivo, using natural, mutated, and/orsynthetic APP substrates, natural, mutated, and/or synthetic enzyme, andthe test compound. The analysis may involve primary or secondary cellsexpressing native, mutant, and/or synthetic APP and enzyme, animalmodels expressing native APP and enzyme, or may utilize transgenicanimal models expressing the substrate and enzyme. Detection ofenzymatic activity can be by analysis of one or more of the cleavageproducts, for example, by immunoassay, flurometric or chromogenic assay,HPLC, or other means of detection. Inhibitory compounds are determinedas those having the ability to decrease the amount of beta-secretasecleavage product produced in comparison to a control, wherebeta-secretase mediated cleavage in the reaction system is observed andmeasured in the absence of inhibitory compounds. Beta-secretase Variousforms of beta-secretase enzyme are known, and are available and usefulfor assay of enzyme activity and inhibition of enzyme activity. Theseinclude native, recombinant, and synthetic forms of the enzyme. Humanbeta-secretase is known as Beta Site APP Cleaving Enzyme (BACE), Asp2,and memapsin 2, and has been characterized, for example, in U.S. Pat.No. 5,744,346 and published PCT patent applications WO98/22597,WO/00/03819, WO01/23533, and WO/0017369, as well as in literaturepublications (Hussain et.al., 1999, Mol.Cell.Neurosci. 14:419-427;Vassar et.al., 1999, Science 286:735-741; Yan et.al., 1999, Nature402:533-537; Sinha et.al., 1999, Nature 40:537-540; and Lin et.al.,2000, PNAS USA 97:1456-1460). Synthetic forms of the enzyme have alsobeen described (WO98/22597 and WO00/17369). Beta-secretase can beextracted and purified from human brain tissue and can be produced incells, for example mammalian cells expressing recombinant enzyme.

[1451] Useful inhibitory compounds are effective to inhibit 50% ofbeta-secretase enzymatic activity at a concentration of less than 50micromolar, preferably at a concentration of IO micromolar or less, morepreferably 1 micromolar or less, and most preferably 10 nanomolar orless.

[1452] APP Substrate

[1453] Assays that demonstrate inhibition of beta-secretase-mediatedcleavage of APP can utilize any of the known forms of APP, including the695 amino acid “normal” isotype described by Kang et.al., 1987, Nature325:733-6, the 770 amino acid isotype described by Kitaguchi et. al.,1981, Nature 331:530-532, and variants such as the Swedish Mutation(KM670-1NL) (APP-SW), the London Mutation (V7176F), and others. See, forexample, U.S. Pat. No. 5,766,846 and also Hardy, 1992, Nature Genet.1:233-234, for a review of known variant mutations. Additional usefulsubstrates include the dibasic amino acid modification, APP-KKdisclosed, for example, in WO 00/17369, fragments of APP, and syntheticpeptides containing the beta-secretase cleavage site, wild type (WT) ormutated form, e.g., SW, as described, for example, in U.S. Pat. No5,942,400 and WO/00/03819.

[1454] The APP substrate contains the beta-secretase cleavage site ofAPP (KM-DA or NL-DA) for example, a complete APP peptide or variant, anAPP fragment, a recombinant or synthetic APP, or a fusion peptide.Preferably, the fusion peptide includes the beta-secretase cleavage sitefused to a peptide having a moiety useful for enzymatic assay, forexample, having isolation and/or detection properties. A useful moietymay be an antigenic epitope for antibody binding, a label or otherdetection moiety, a binding substrate, and the like.

[1455] Antibodies

[1456] Products characteristic of APP cleavage can be measured byimmunoassay using various antibodies, as described, for example, inPirttila et.al., 1999, Neuro.Lett. 249:21-4, and in U.S. Pat.No.5,612,486. Useful antibodies to detect A beta include, for example,the monoclonal antibody 6E10 (Senetek, St. Louis, Mo.) that specificallyrecognizes an epitope on amino acids 1-16 of the A beta peptide;antibodies 162 and 164 (New York State Institute for Basic Research,Staten Island, N.Y.) that are specific for human A beta 1-40 and 1-42,respectively; and antibodies that recognize the junction region ofbeta-amyloid peptide, the site between residues 16 and 17, as describedin U.S. Pat. No. 5,593,846. Antibodies raised against a syntheticpeptide of residues 591 to 596 of APP and SW 192 antibody raised against590-596 of the Swedish mutation are also useful in immunoassay of APPand its cleavage products, as described in U.S. Pat. Nos. 5,604,102 and5,721,130.

[1457] Assay Systems

[1458] Assays for determining APP cleavage at the beta-secretasecleavage site are well known in the art. Exemplary assays, aredescribed, for example, in U.S. Pat. Nos. 5,744,346 and 5,942,400, anddescribed in the Examples below.

[1459] Cell Free Assays

[1460] Exemplary assays that can be used to demonstrate the inhibitoryactivity of the compounds of the invention are described, for example,in WO00/17369, WO 00/03819, and U.S. Pat. Nos. 5,942,400 and 5,744,346.Such assays can be performed in cell-free incubations or in cellularincubations using cells expressing a beta-secretase and an APP substratehaving a beta-secretase cleavage site.

[1461] An APP substrate containing the beat-secretase cleavage site ofAPP, for example, a complete APP or variant, an APP fragment, or arecombinant or synthetic APP substrate containing the amino acidsequence: KM-DA or NL-DA, is incubated in the presence of beta-secretaseenzyme, a fragment thereof, or a synthetic or recombinant polypeptidevariant having beta-secretase activity and effective to cleave thebeta-secretase cleavage site of APP, under incubation conditionssuitable for the cleavage activity of the enzyme. Suitable substratesoptionally include derivatives that may be fusion proteins or peppidesthat contain the substrate peptide and a modification useful tofacilitate the purification or detection of the peptide or itsbeta-secretase cleavage products. Useful modifications include theinsertion of a known antigenic epitope for antibody binding; the linkingof a label or detectable moiety, the linking of a binding substrate, andthe like.

[1462] Suitable incubation conditions for a cell-free in vitro assayinclude, for example: approximately 200 nanomolar to 10 micromolarsubstrate, approximately 10 to 200 picomolar enzyme, and approximately0.1 nanomolar to 10 micromolar inhibitor compound, in aqueous solution,at an approximate pH of 4-7, at approximately 37 degrees C., for a timeperiod of approximately 10 minutes to 3 hours. These incubationconditions are exemplary only, and can be varied as required for theparticular assay components and/or desired measurement system.Optimization of the incubation conditions for the particular assaycomponents should account for the specific beta-secretase enzyme usedand its pH optimum, any additional enzymes and/or markers that might beused in the assay, and the like. Such optimization is routine and willnot require undue experimentation.

[1463] One useful assay utilizes a fusion peptide having maltose bindingprotein (MBP) fused to the C-terminal 125 amino acids of APP-SW. The MBPportion is captured on an assay substrate by anti-MBP capture antibody.Incubation of the captured fusion protein in the presence ofbeta-secretase results in cleavage of the substrate at thebeta-secretase cleavage site. Analysis of the cleavage activity can be,for example, by immunoassay of cleavage products. One such immunoassaydetects a unique epitope exposed at the carboxy terminus of the cleavedfusion protein, for example, using the antibody SW192. This assay isdescribed, for example, in U.S. Pat. No 5,942,400.

[1464] Cellular Assay

[1465] Numerous cell-based assays can be used to analyze beta-secretaseactivity and/or processing of APP to release A beta. Contact of an APPsubstrate with a beta-secretase enzyme within the cell and in thepresence or absence of a compound inhibitor of the invention can be usedto demonstrate beta-secretase inhibitory activity of the compound.Preferably, assay in the presence of a useful inhibitory compoundprovides at least about 30%, most preferably at least about 50%inhibition of the enzymatic activity, as compared with a non-inhibitedcontrol.

[1466] In one embodiment, cells that naturally express beta-secretaseare used. Alternatively, cells are modified to express a recombinantbeta-secretase or synthetic variant enzyme as discussed above. The APPsubstrate may be added to the culture medium and is preferably expressedin the cells. Cells that naturally express APP, variant or mutant formsof APP, or cells transformed to express an isoform of APP, mutant orvariant APP, recombinant or synthetic APP, APP fragment, or syntheticAPP peptide or fusion protein containing the beta-secretase APP cleavagesite can be used, provided that the expressed APP is permitted tocontact the enzyme and enzymatic cleavage activity can be analyzed.

[1467] Human cell lines that normally process A beta from APP provide auseful means to assay inhibitory activities of the compounds of theinvention. Production and release of A beta and/or other cleavageproducts into the culture medium can be measured, for example byimmunoassay, such as Western blot or enzyme-linked immunoassay (EIA)such as by ELISA.

[1468] Cells expressing an APP substrate and an active beta-secretasecan be incubated in the presence of a compound inhibitor to demonstrateinhibition of enzymatic activity as compared with a control. Activity ofbeta-secretase can be measured by analysis of one or more cleavageproducts of the APP substrate. For example, inhibition of beta-secretaseactivity against the substrate APP would be expected to decrease releaseof specific beta-secretase induced APP cleavage products such as A beta.

[1469] Although both neural and non-neural cells process and release Abeta, levels of endogenous beta-secretase activity are low and oftendifficult to detect by EIA. The use of cell types known to have enhancedbeta-secretase activity, enhanced processing of APP to A beta, and/orenhanced production of A beta are therefore preferred. For example,transfection of cells with the Swedish Mutant form of APP (APP-SW); withAPP-KK; or with APP-SW-KK provides cells having enhanced beta-secretaseactivity and producing amounts of A beta that can be readily measured.

[1470] In such assays, for example, the cells expressing APP andbeta-secretase are incubated in a culture medium under conditionssuitable for beta-secretase enzymatic activity at its cleavage site onthe APP substrate. On exposure of the cells to the compound inhibitor,the amount of A beta released into the medium and/or the amount of CTF99fragments of APP in the cell lysates is reduced as compared with thecontrol. The cleavage products of APP can be analyzed, for example, byimmune reactions with specific antibodies, as discussed above.

[1471] Preferred cells for analysis of beta-secretase activity includeprimary human neuronal cells, primary transgenic animal neuronal cellswhere the transgene is APP, and other cells such as those of a stable293 cell line expressing APP, for example, APP-SW.

[1472] In Vivo Assays: Animal Models

[1473] Various animal models can be used to analyze beta-secretaseactivity and /or processing of APP to release A beta, as describedabove. For example, transgenic animals expressing APP substrate andbeta-secretase enzyme can be used to demonstrate inhibitory activity ofthe compounds of the invention. Certain transgenic animal models havebeen described, for example, in U.S. Pat. Nos. 5,877,399; 5,612,486;5,387,742; 5,720,936; 5,850,003; 5,877,015,, and 5,811,633, and in Ganeset.al., 1995, Nature 373:523. Preferred are animals that exhibitcharacteristics associated with the pathophysiology of AD.Administration of the compound inhibitors of the invention to thetransgenic mice described herein provides an alternative method fordemonstrating the inhibitory activity of the compounds. Administrationof the compounds in a pharmaceutically effective carrier and via anadministrative route that reaches the target tissue in an appropriatetherapeutic amount is also preferred.

[1474] Inhibition of beta-secretase mediated cleavage of APP at thebeta-secretase cleavage site and of A beta release can be analyzed inthese animals by measure of cleavage fragments in the animal's bodyfluids such as cerebral fluid or tissues. Analysis of brain tissues forA beta deposits or plaques is preferred.

[1475] On contacting an APP substrate with a beta-secretase enzyme inthe presence of an inhibitory compound of the invention and underconditions sufficient to permit enzymatic mediated cleavage of APPand/or release of A beta from the substrate, the compounds of theinvention are effective to reduce beta-secretase-mediated cleavage ofAPP at the beta-secretase cleavage site and/or effective to reducereleased amounts of A beta. Where such contacting is the administrationof the inhibitory compounds of the invention to an animal model, forexample, as described above, the compounds are effective to reduce Abeta deposition in brain tissues of the animal, and to reduce the numberand/or size of beta amyloid plaques. Where such administration is to ahuman subject, the compounds are effective to inhibit or slow theprogression of disease characterized by enhanced amounts of A beta, toslow the progression of AD in the, and/or to prevent onset ordevelopment of AD in a patient at risk for the disease.

[1476] Unless defined otherwise, all scientific and technical terms usedherein have the same meaning as commonly understood by one of skill inthe art to which this invention belongs. All patents and publicationsreferred to herein are hereby incorporated by reference for allpurposes.

DEFINITIONS AND CONVENTIONS

[1477] The definitions and explanations below are for the terms as usedthroughout this entire document including both the specification and theclaims.

I. CONVENTIONS FOR FORMULAS AND DEFINITIONS OF VARIABLES

[1478] The chemical formulas representing various compounds or molecularfragments in the specification and claims may contain variablesubstituents in addition to expressly defined structural features. Thesevariable substituents are identified by a letter or a letter followed bya numerical subscript, for example, “Z₁” or “R_(i)” where “i” is aninteger. These variable substituents are either monovalent or bivalent,that is, they represent a group attached to the formula by one or twochemical bonds. For example, a group Z₁ would represent a bivalentvariable if attached to the formula CH₃—C(═Z₁)H. Groups R_(i) and R_(j)would represent monovalent variable substituents if attached to theformula CH₃—CH₂—C(R_(i))(R_(j))H₂. When chemical formulas are drawn in alinear fashion, such as those above, variable substituents contained inparentheses are bonded to the atom immediately to the left of thevariable substituent enclosed in parentheses. When two or moreconsecutive variable substituents are enclosed in parentheses, each ofthe consecutive variable substituents is bonded to the immediatelypreceding atom to the left which is not enclosed in parentheses. Thus,in the formula above, both R_(i) and R_(j) are bonded to the precedingcarbon atom. Also, for any molecule with an established system of carbonatom numbering, such as steroids, these carbon atoms are designated asC_(i), where “i” is the integer corresponding to the carbon atom number.For example, C₆ represents the 6 position or carbon atom number in thesteroid nucleus as traditionally designated by those skilled in the artof steroid chemistry. Likewise the term “R₆” represents a variablesubstituent (either monovalent or bivalent) at the C₆ position.

[1479] Chemical formulas or portions thereof drawn in a linear fashionrepresent atoms in a linear chain. The symbol “—” in general representsa bond between two atoms in the chain. Thus CH₃—O—CH₂—CH(R_(i))—CH₃represents a 2-substituted-1-methoxypropane compound. In a similarfashion, the symbol “═” represents a double bond, e.g.,CH₂═C(R_(i))—O—CH₃, and the symbol “≡” represents a triple bond, e.g.,HC≡C—CH(R_(i))—CH₂—CH₃. Carbonyl groups are represented in either one oftwo ways: —CO— or —C(═O)—, with the former being preferred forsimplicity.

[1480] Chemical formulas of cyclic (ring) compounds or molecularfragments can be represented in a linear fashion. Thus, the compound4-chloro-2-methylpyridine can be represented in linear fashion byN*═C(CH₃)—CH═CC₁—CH═C*H with the convention that the atoms marked withan asterisk (*) are bonded to each other resulting in the formation of aring. Likewise, the cyclic molecular fragment, 4-(ethyl)-1-piperazinylcan be represented by —N*—(CH₂)₂—N(C₂H₅)—CH₂—C*H₂.

[1481] A rigid cyclic (ring) structure for any compounds herein definesan orientation with respect to the plane of the ring for substituentsattached to each carbon atom of the rigid cyclic compound. For saturatedcompounds which have two substituents attached to a-carbon atom which ispart of a cyclic system, —C(X₁)(X₂)— the two substituents may be ineither an axial or equatorial position relative to the ring and maychange between axial/equatorial. However, the position of the twosubstituents relative to the ring and each other remains fixed. Whileeither substituent at times may lie in the plane of the ring(equatorial) rather than above or below the plane (axial), onesubstituent is always above the other. In chemical structural formulasdepicting such compounds, a substituent (XI) which is “below” anothersubstituent (X₂) will be identified as being in the alpha configurationand is identified by a broken, dashed or dotted line attachment to thecarbon atom, i.e., by the symbol “ - - - ” or “ . . . ”. Thecorresponding substituent attached “above” (X₂) the other (Xx₁) isidentified as being in the beta configuration and is indicated by anunbroken line attachment to the carbon atom.

[1482] When a variable substituent is bivalent, the valences may betaken together or separately or both in the definition of the variable.For example, a variable R_(i) attached to a carbon atom as —C(═R₁)—might be bivalent and be defined as oxo or keto (thus forming a carbonylgroup (—CO—) or as two separately attached monovalent variablesubstituents alpha-R_(i-j) and beta-R_(i-k). When a bivalent variable,R_(i), is defined to consist of two monovalent variable substituents,the convention used to define the bivalent variable is of the form“alpha-R_(i-j):beta-R_(i-k)” or some variant thereof. In such a caseboth alpha-R_(i-j) and beta-R_(i-k) are attached to the carbon atom togive —C(alpha-R_(i-j))(beta-R_(i-k))—. For example, when the bivalentvariable R₆, —C(═R₆)— is defined to consist of two monovalent variablesubstituents, the two monovalent variable substituents arealpha-R₆₋₁:beta-R₆₋₂, . . . alpha-R₆₋₉:beta-R₆₋₁₀, etc, giving-C(alpha-R₆₋₁)(beta-R₆₋₂)—, . . . —C(alpha-R₆₋₉)(beta-R₆₋₁₀)—, etc.Likewise, for the bivalent variable R₁₁, —C(═R₁₁)—, two monovalentvariable substituents are alpha-R₁₁₋₁:beta-R₁₁₋₂. For a ring substituentfor which separate alpha and beta orientations do not exist (e.g. due tothe presence of a carbon carbon double bond in the ring), and for asubstituent bonded to a carbon atom which is not part of a ring theabove convention is still used, but the alpha and beta designations areomitted.

[1483] Just as a bivalent variable may be defined as two separatemonovalent variable substituents, two separate monovalent variablesubstituents may be defined to be taken together to form a bivalentvariable. For example, in the formula —C₁(R_(i))H—C₂(R_(j))H— (C₁ and C₂define arbitrarily a first and second carbon atom, respectively) R_(i)and R_(j) may be defined to be taken together to form (1) a second bondbetween C₁ and C₂ or (2) a bivalent group such as oxa (—O—) and theformula thereby describes an epoxide. When R_(i) and R_(j) are takentogether to form a more complex entity, such as the group —X—Y—, thenthe orientation of the entity is such that C, in the above formula isbonded to X and C₂ is bonded to Y. Thus, by convention the designation“. . . R_(i) and R_(j) are taken together to form —CH₂—CH₂—O—CO—. . . ”means a lactone in which the carbonyl is bonded to C₂. However, whendesignated “. . . R_(j) and R_(i) are taken together to form—CO—O—CH₂—CH₂— the convention means a lactone in which the carbonyl isbonded to C₁.

[1484] The carbon atom content of variable substituents is indicated inone of two ways. The first method uses a prefix to the entire name ofthe variable such as “C₁-C₄”, where both “1” and “4” are integersrepresenting the minimum and maximum number of carbon atoms in thevariable. The prefix is separated from the variable by a space. Forexample, “C₁-C₄ alkyl” represents alkyl of 1 through 4 carbon atoms,(including isomeric forms thereof unless an express indication to thecontrary is given). Whenever this single prefix is given, the prefixindicates the entire carbon atom content of the variable being defined.Thus C₂-C₄ alkoxycarbonyl describes a group CH₃—(CH₂)_(n)—O—CO— where nis zero, one or two. By the second method the carbon atom content ofonly each portion of the definition is indicated separately by enclosingthe “C_(i)-C_(j)” designation in parentheses and placing it immediately(no intervening space) before the portion of the definition beingdefined. By this optional convention (C₁-C₃)alkoxycarbonyl has the samemeaning as C₂-C₄ alkoxycarbonyl because the “C₁-C₃” refers only to thecarbon atom content of the alkoxy group. Similarly while both C₂-C₆alkoxyalkyl and (C₁-C₃)alkoxy(C₁-C₃)alkyl define alkoxyalkyl groupscontaining from 2 to 6 carbon atoms, the two definitions differ sincethe former definition allows either the alkoxy or alkyl portion alone tocontain 4 or 5 carbon atoms while the latter definition limits either ofthese groups to 3 carbon atoms.

[1485] When the claims contain a fairly complex (cyclic) substituent, atthe end of the phrase naming/designating that particular substituentwill be a notation in (parentheses) which will correspond to the samename/designation in one of the CHARTS which will also set forth thechemical structural formula of that particular substituent.

II. DEFINITIONS

[1486] All temperatures are in degrees Celsius.

[1487] TLC refers to thin-layer chromatography. psi refers topounds/in².

[1488] HPLC refers to high pressure liquid chromatography.

[1489] THF refers to tetrahydrofuran.

[1490] DMF refers to dimethylformamide.

[1491] EDC refers to ethyl-1-(3-dimethylaminopropyl)carbodiimide or1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[1492] HOBt refers to 1-hydroxy benzotriazole hydrate.

[1493] NMM refers to N-methylmorpholine.

[1494] NBS refers to N-bromosuccinimide.

[1495] TEA refers to triethylamine.

[1496] BOC refers to 1,1-dimethylethoxy carbonyl or t-butoxycarbonyl,—CO—O—C(CH₃)₃.

[1497] CBZ refers to benzyloxycarbonyl, —CO—O—CH₂-phenyl.

[1498] FMOC refers to 9-fluorenylmethyl carbonate.

[1499] TFA refers to trifluoracetic acid, CF₃—COOH.

[1500] CDI refers to 1,1′-carbonyldiimidazole.

[1501] Saline refers to an aqueous saturated sodium chloride solution.

[1502] Chromatography (column and flash chromatography) refers topurification/separation of compounds expressed as (support, eluent). Itis understood that the appropriate fractions are pooled and concentratedto give the desired compound(s).

[1503] CMR refers to C-13 magnetic resonance spectroscopy, chemicalshifts are reported in ppm (δ) downfield from TMS.

[1504] NMR refers to nuclear (proton) magnetic resonance spectroscopy,chemical shifts are reported in ppm (d) downfield from TMS.

[1505] IR refers to infrared spectroscopy.

[1506] -phenyl refers to phenyl (C₆H₅).

[1507] MS refers to mass spectrometry expressed as m/e, m/z ormass/charge unit. MH⁺ refers to the positive ion of a parent plus ahydrogen atom. EI refers to electron impact. CI refers to chemicalionization. FAB refers to fast atom bombardment.

[1508] HRMS refers to high resolution mass spectrometry.

[1509] Ether refers to diethyl ether.

[1510] Pharmaceutically acceptable refers to those properties and/orsubstances which are acceptable to the patient from apharmacological/toxicological point of view and to the manufacturingpharmaceutical chemist from a physical/chemical point of view regardingcomposition, formulation, stability, patient acceptance andbioavailability.

[1511] When solvent pairs are used, the ratios of solvents used arevolume/volume (v/v).

[1512] When the solubility of a solid in a solvent is used the ratio ofthe solid to the solvent is weight/volume (wt/v).

[1513] BOP refers to benzotriazol-1-yloxy-tris(dimethylamino)phosphoniumhexafluorophosphate.

[1514] TBDMSCI refers to t-butyldimethylsilyl chloride.

[1515] TBDMSOTf refers to t-butyldimethylsilyl trifluosulfonic acidester.

[1516] Trisomy 21 refers to Down's Syndrome.

[1517] The following terms are used (in EXAMPLEs 321 and above) for theamide forming agent (IX):

[1518] “PHTH” refers to (CH₃—CH₂—CH₂—)₂N—CO-phenyl-CO—OH where theattachment to the -phenyl-ring is 1,3-;

[1519] “5-Me-PHTH” refers to (CH₃—CH₂—CH₂—)₂N—CO—(CH₃—) phenyl —CO—OHwhere the attachment to the -phenyl-ring is 1,3- for the carbonyl groupsand 5- for the methyl group;

[1520] “3,5-pyridinyl” refers to (CH₃—CH₂—CH₂—)₂N—CO—(pyridinyl) —CO—OHwhere the attachment to the -pyridinyl-ring is 3,5- for the carbonylgroups;

[1521] “—SO₂—” refers to (CH₃—CH₂—CH₂—)₂CH-SO₂-phenyl —CO—OH where theattachment to the -phenyl-ring is 1,3-;

[1522] “5-OMe-PHTH” refers to (CH₃—CH₂—CH₂—)₂N—CO—(CH₃—O—) phenyl —CO—OHwhere the attachment to the -phenyl-ring is 1,3- for the carbonyl groupsand 5- for the methoxy group;

[1523] “5-C₁-PHTH” refers to (CH₃—CH₂—CH₂—)₂N—CO—(Cl—)phenyl-CO—OH wherethe attachment to the -phenyl-ring is 1,3- for the carbonyl groups and5- for the chlorine atom;

[1524] “5-F-PHTH” refers to (CH₃—CH₂—CH₂—)₂N—CO—(F—)phenyl-CO—OH wherethe attachment to the -phenyl-ring is 1,3- for the carbonyl groups and5- for the fluorine atom;

[1525] “thienyl” refers to (CH₃—CH₂—CH₂—)₂N—CO-thienyl-CO—OH where theattachment to the thiophene ring is -2,5;

[1526] “2,4-pyridinyl” refers to (CH₃—CH₂—CH₂—)₂N—CO—(pyridinyl) —CO—OHwhere the attachment to the -pyridinyl-ring is 2,4- for the carbonylgroups;

[1527] “4,6-pyrimidinyl” refers to(CH₃—CH₂—CH₂—)₂N—CO—(pyrimidinyl-)phenyl-CO—OH where the attachment tothe -pyrimidiny-1 ring is 4,6- for the carbonyl groups;

[1528] “morpholinyl” refers to morpholinyl-CO-phenyl-CO—OH where theattachment to the -phenyl-ring is 1,3 for the carbonyl groups.

[1529] APP, amyloid precursor protein, is defined as any APPpolypeptide, including APP variants, mutations, and isoforms, forexample, as disclosed in U.S. Pat. No. 5,766,846.

[1530] A beta, amyloid beta peptide, is defined as any peptide resultingfrom beta-secretase mediated cleavage of APP, including peptides of 39,40, 41, 42, and 43 amino acids, and extending from the beta-secretasecleavage site to amino acids 39, 40, 41, 42, or 43.

[1531] Beta-secretase (BACE1, Asp2, Memapsin 2) is an aspartyl proteasethat mediates cleavage of APP at the amino-terminal edge of A beta.Human beta-secretase is described, for example, in WO/001 7369.

[1532] “Pharmaceutically acceptable” refers to those properties and/orsubstances that are acceptable to the patient from apharmacological/toxicological point of view and to the manufacturingpharmaceutical chemist from a physical/chemical point of view regardingcomposition, formulation, stability, patient acceptance andbioavailability.

[1533] A therapeutically effective amount is defined as an amounteffective to reduce or lessen at least one symptom of the disease beingtreated or to reduce or delay onset of one or more clinical markers orsymptoms of the disease.

[1534] The present invention provides compounds, compositions, andmethods for inhibiting beta-secretase enzyme activity and A beta peptideproduction. Inhibition of beta-secretase enzyme activity halts orreduces the production of A beta from APP and reduces or eliminates theformation of beta-amyloid deposits in the brain.

EXAMPLES

[1535] Without further elaboration, it is believed that one skilled inthe art can, using the preceding description, practice the presentinvention to its fullest extent. The following detailed examplesdescribe how to prepare the various compounds and/or perform the variousprocesses of the invention and are to be construed as merelyillustrative, and not limitations of the preceding disclosure in any waywhatsoever. Those skilled in the art will promptly recognize appropriatevariations from the procedures both as to reactants and as to reactionconditions and techniques.

[1536] Preparation 1

[1537] 3-Amino-5-(methoxycarbonyl)Benzoic Acid (XVII)

[1538] A suspension of mono-methyl 5-nitro-isophthalate (22.5 g, 100mmol) and palladium on carbon (5%, 2.00 g) in methanol (100 mL) isshaken in a hydrogenation apparatus under hydrogen (50 psi) for 3 hours.The mixture is then filtered through diatomaceous earth and concentratedto give the title compound, NMR (300 MHz, CDCl₃) delta 7.67, 7.41, 7.40and 3.83; MS (ESI−) for C₉H₉NO₄ m/z (M−H)⁻=194.

[1539] Preparation 2

[1540] 3-Bromo-5-(methoxycarbonyl)Benzoic Acid (XIX)

[1541] A mixture of copper (II) bromide (1.85 g, 8.30 mmol), n-butylnitrite (1.07 g, 10.4 mmol), and acetonitrile (30 mL) is stirred in around bottomed flask in a water bath to which a few chunks of ice hasbeen added. 3-Amino-5-(methoxycarbonyl)benzoic acid (XVII, PREPARATION1, 1.35 g, 6.92 mmol) is added as a slurry in warm acetonitrile (70 mL)over 15 min and the mixture is stirred at 20-25 degrees C. for anadditional 2 hour, at which time the mixture is partitioned betweendichloromethane and hydrochloric acid (3N). The organic phase isseparated and dried over sodium sulfate and concentrated to dryness.Chromatography (silica gel, 125 mL; methanol/dichloromethane, 15/85) andconcentration of the appropriate fractions gives a solid which iscrytallized from methanol to give the title compound in two crops, NMR(DMSO-d₆) delta 3.90, 8.26 and 8.65.

[1542] Preparation 3

[1543] Methyl 3-bromo-5-[(dipropylamino)carbonyl]benzoate (XXI)

[1544] Carbonyl diimidazole (3-0 g, 18 mmol) is added to a solution of3-bromo-5-(methoxycarbonyl)benzoic acid (XIX, PREPARATION 2, 3.9 g, 15mmol) in THF (30 mL). The mixture is stirred for 0.5 hours.Dipropylamine (AMINE, 4.2 mL, 30 mmol) is added to the mixture, which isthen stirred for 24 hours. The solvent is then removed under reducedpressure and the mixture is partitioned between ethyl acetate and water.The organic phase is then washed with saline, dried over anhydrousmagnesium sulfate, filtered, and concentrated. Column chromatography(silica gel; ethyl acetate/hexanes, 15/85) gives the title compound, IR(diffuse reflectance) 2968, 2958, 1714, 1637, 1479, 1440, 1422, 1321,1310, 1288, 1273, 1252, 889, 772 and 718 cm⁻¹; NMR (300 MHz, CDCl₃) δ8.21, 7.96, 7.70, 3.95, 3.46, 3.15, 1.69, 1.57, 1.00 and 0.78; MS (ESI+)for C₁₅H₂₀BrNO₃ m/z (M+H)⁺=344.1.

[1545] Preparation 4

[1546] 3-Bromo-5-[(dipropylamino)carbonyl]Benzoic Acid

[1547] To a solution of methyl3-bromo-5-[(dipropylamino)carbonyl]benzoate (XXI, PREPARATION 3, 1.4 g,4.1 mmol) in THF/water/methanol (4/2/2, 8 mL) is added to lithiumhydroxide monohydrate (0.17 g, 4.05 mmol). The mixture is stirred at 20degrees −25 degrees C. for 1 hour and then solvent is removed underreduced pressure. The residue is dissolved in water (50 mL) andhydrochloric acid (1 N) is added to adjust the pH to about 3. Theaqueous mixture is extracted with ethyl acetate and the organic phase isseparated and dried over magnesium sulfate to give the title compound.Analytical calculated for C₁₄H₁₈BrNO₃: C, 51.23;H, 5.53; N, 4.27; Br,24.35. Found: C, 51.37;H, 5.56; N, 4.28.

[1548] Preparation 5

[1549] Methyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]-benzoate(XXII)

[1550] To a mixture of methyl3-bromo-5-[(dipropylamino)carbonyl]benzoate (XXI, PREPARATION 3, 0.5 g,1.47 mmol) in dry N-methyl pyrrolidinone under a carbon monoxideatmosphere is added palladium (II) acetate (0.017 g, 0.074 mmol),1,3-bis(diphenylphosphino)propane (0.045 g, 0.11 mmol),hexamethyldisilazane (1.0 mL, 4.7 mmol), and diisopropylethylamine (0.38g, 2.94 mmol). The mixture is heated at 100 degrees C. for 24 hours. Themixture is cooled to 20-25 degrees C. and partitioned between water andethyl acetate. The layers are separated and the aqueous phase isback-washed with ethyl acetate. The organic phases are combined andwashed three times with saline, dried over anhydrous magnesium sulfate,filtered and concentrated. Column chromatography (silica gel, 75 mL;methanol/methylene chloride, 2.5/97.5) gives the title compound, NMR(CDCl₃) delta 0.77, 1.02, 1.57, 1.71, 3.17, 3.49, 3.98, 5.78, 6.34,8.07, 8.20 and 8.48.

[1551] Preparation 6

[1552] 3-(Aminocarbonyl)-5-[(dipropylamino)carbonyl]Benzoic Acid (XXIII)

[1553] To a mixture of methyl3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate (XXII, PREPARATION5, 0.197 g, 0.64 mmol) in methanol (5.0 mL) is added sodium hydroxide(1N, 3.0 mL). The mixture is stirred at 20-25 degrees C. for 24 hours.The mixture is acidified to about pH 5 with hydrochloric acid (10%).Water (50 mL) is added and the mixture is washed twice with ethylacetate (2×50 mL). The organic extracts are combined and dried overanhydrous magnesium sulfate and concentrated to give the title compound,NMR (DMSO-d₆) delta 0.66, 0.930, 1.48, 1.62, 3.12, 3.35, 7.54, 7.98,8.22 and 8.51.

[1554] Preparation 7

[1555] 3-Cyano-5-[(dipropylamino)carbonyl]Benzoic Acid (IX/XXXII)

[1556] A mixture of 3-bromo-5-[(dipropylamino)carbonyl]benzoic acid(PREPARATION 4, 0.596 g, 1.82 mmol) and copper nitrile (0.325 g, 3.63mmol) in N-methylpyrrolidinone (1.5 mL) is stirred at 175 degrees C. for2.5 hour, at which time the mixture is cooled and partitioned betweenethyl acetate and hydrochloric acid (3N). The organic layer is washedtwice more with hydrochloric acid (3N) and then twice more with salinewhich had been acidified with a small amount of hydrochloric acid (3N).The organic layer is dried over magnesium sulfate and concentrated underhigh vacuum to give the title compound, NMR (CDCl₃) delta 0.80, 1.02,1.60, 1.73, 3.17, 3.51, 7.90, 8.31 and 8.41; an aliquot is crystallizedfrom ethyl ether/dichloromethane/hexane —IR (diffuse reflectance) 3017,2970, 2937, 2898, 2877, 2473, 2432, 2350, 2318, 2236, 1721, 1608, 1588,1206 and 1196 cm⁻¹.

[1557] Preparation 8

[1558] 3-(Aminocarbonyl)-5-[(dipropylamino)carbonyl]Benzoic Acid(XXXIII)

[1559] A mixture of 3-cyano-5-[(dipropylamino)carbonyl]benzoic acid(IX/XXXII, PREPARATION 7, 0.602 g, 2.19 mmol), potassium carbonate(0.212 g, 1.53 mmol), and acetone (2.5 mL) is stirred at 20-25 degreesC. Water (2.5 mL) and urea-hydrogen peroxide adduct (0.825 g, 8.78 mmol)are added and the mixture is stirred for 15 hours at 20-25 degrees C.,at which time additional urea-hydrogen peroxide adduct (0.204 g) isadded; after stirring for another 3 hours, an additional 0.205 g ofurea-hydrogen peroxide is added. After a total of 39 hours has elapsed,the acetone is removed under reduced pressure and the residue isacidified with hydrochloric acid (3N) to pH=2-4. The mixture isextracted with dichloromethane, the organic layer is separated andwashed with hydrochloric acid (0.5 N), and the organic phase is driedwith anhydrous magnesium sulfate to a solid. The solid is crystallizedfrom dichloromethane/hexane/methanol to give the title compound, MS(ESI+) for C₁₅H₂₀N₂O₄ m/z (M+H)⁺=293.2.

[1560] Preparation 9

[1561] Methyl 3-[(dipropylamino)carbonyl]-5-nitrobenzoate (XXX)

[1562] Carbonyl diimidazole (3.90 g, 24.0 mmol) is added to a mixture ofmono-methyl 5-nitro-isophthalate (XXVIII, 4.50 g, 20.0 mmol) in dry THF(50 mL). The mixture is stirred for 0.5 hours. Dipropylamine (3.28 mL,24.0 mmol) is added slowly to the mixture. The reaction mixture is thenstirred for 4 hours. The solvent is removed under reduced pressure andthe mixture is partitioned between ethyl acetate and water. The organicphase is separated and washed with saline, dried over anhydrous sodiumsulfate, filtered, and concentrated. Column chromatography (silica gel;ethyl acetate/hexanes, 15/85) gives the title compound, NMR (300 MHz,CDCl₃) delta 8.88, 8.41, 8.35, 4.00, 3.48, 3.15, 1.72, 1.57, 1.00 and0.77; MS (ESI+) for C₁₅H₂₀N₂O₅ m/z (M+H)⁺=309.2.

[1563] Preparation 10

[1564] Methyl 3-amino-5-[(dipropylamino)carbonyl]Benzoate (XXXI)

[1565] A suspension of methyl3-[(dipropylamino)carbonyl]-5-nitrobenzoate (XXX, PREPARATION 9, 6.00g,20.0 mmol) and palladium on carbon (5%, 0.600 g) in methanol (40 mL) isshaken in a hydrogenation apparatus under hydrogen (45 psi) for 3 hours.The mixture is then filtered through diatomaceous earth and concentratedto give the title compound, NMR (300 MHz, CDCl₃) delta 7.27, 6.77, 4.10,3.82, 3.38, 3.10, 1.62, 1.46, 0.91 and 0.68.

[1566] Preparation 11

[1567] Methyl 3-(chlorosulfonyl)-5-[(dipropylamino)carbonyl]-Benzoate(XXXVII)

[1568] Methyl 3-amino-5-[(dipropylamino)carbonyl]Benzoate (XXXI,PREPARATION 10, 1.11 g, 4 mmol) is added to a mixture of water (5 mL)and concentrated hydrochloric acid (1 mL). Sodium nitrite (0.276 g, 4mmol) is added to the mixture slowly at 0 degrees C. The mixture is thenadded to an acetic acid solution (5 mL) of CuCl₂.2H₂O saturated withsulfur dioxide. The mixture is stirred for 0.5 hours and poured into icewater. The mixture is extracted with ethyl acetate. The organic phase isseparated and washed with saturated sodium bicarbonate, water, andsaline and dried over anhydrous sodium sulfate, filtered, andconcentrated to give the title compound, NMR (300 MHz, CDCl₃) delta8.69, 8.38, 8.20,4.01, 3.49, 3.14, 1.72,1.59, 1.01 and 0.79; MS (ESI+)for C₁₅H₂₀CINO₅S m/z (M+H)⁺=362.2.

[1569] Preparation 12

[1570] Methyl 3-(aminosulfonyl)-5-[(dipropylamino)carbonyl]-Benzoate(XXXVIII)

[1571] To a solution of methyl3-(chlorosulfonyl)-5-[(dipropylamino)carbonyl]benzoate (XXXVII,PREPARATION 11, 0.100 g, 0.300 mmol) in dry THF (3 mL) is added ammonia(7 N solution in methanol, 0.214 mL, 1.50 mmol). The mixture is stirredfor 18 hours and solvent is then removed. The residue is partitionedbetween ethyl acetate and water. The organic phase is separate andwashed with saline, dried over anhydrous sodium sulfate, filtered, andconcentrated to give the title compound, NMR (300 MHz, CDCl₃) delta8.45, 8.07, 8.01, 6.05, 3.93, 3.44, 3.09, 1.67, 1.52, 0.96 and 0.73; MS(ESI+) for C₁₂H₂₂N₂O₅S m/z (M+H)⁺=343.3.

[1572] Preparation 13

[1573] 3-(Aminosulfonyl)-5-[(dipropylamino)carbonyl]Benzoic Acid(XXXVIII)

[1574] Lithium hydroxide monohydrate (0.011 g, 0.263 mmol) is added to asolution of methyl 3-(aminosulfonyl)-5-[(dipropylamino)carbonyl]benzoate(XXXVIII, PREPARATION 12, 0.090 g, 0.263 mmol) in a mixture ofTHF/methanol/water (2/1/1, 2 mL). The mixture is stirred at 20-25degrees C. for 3 hours. The mixture is then diluted with water andhydrochloric acid (1 N) is added to bring the pH to less than 3. Theaqueous solution is extracted with ethyl acetate. The organic phase isseparated and washed with saline, dried over anhydrous sodium sulfate,filtered and concentrated to give the title compound. ¹H NMR (300 MHz,CDCl₃) delta 10.36 (s, 1H), 8.39 (s, 1H), 8.09 (s, 2H), 6.06 (s, 2H),3.48 (t, J=7 Hz, 2H), 3.15 (t, J=7 Hz, 2H), 1.71 (m, 2H), 1.55 (m, 2H),0.97 (t, J=7 Hz, 31H), 0.74 (t, J=7 Hz, 3H). MS (ESI+) for C₁₁H₂₀N₂O₅Sm/z 329.2 (M+H)⁺.

[1575] Preparation 14

[1576] Methyl3-[(dipropylamino)carbonyl]-5-(1-pyrrolidinylsulfonyl)-Benzoate(XXXVIII)

[1577] Following the general procedure of PREPARATION 12 and makingnon-critical variations but using pyrrolidine (0.347 mL, 4.16 mmol), thetitle compound is obtained, MS (ESI+) for Cl₉H₂₈N₂O₅S m/z (M+H)⁺=397.1.

[1578] Preparation 15

[1579] 3-[(Dipropylamino)carbonyl]-5-(1-pyrrolidinylsulfonyl)BenzoicAcid (XXXIX)

[1580] Following the general procedure of PREPARATION 13 and makingnon-critical variations, the title compound is obtained, MS (ESI+) forC₁₈H₂₆N₂O₅S m/z (M+H)⁺=383.3.

[1581] Preparation 16

[1582] Methyl3-[(dipropylamino)carbonyl]-5-[(methylamino)-sulfonyl]benzoate (XXXVIII)

[1583] Following the general procedure of PREPARATION 12 and makingnon-critical variations but using methyl amine (2 N solution in THF,0.692 mL, 1.38 mmol), the title compound is obtained, MS (ESI+) forC₁₆H₂₄N₂O₅S m/z (M+H)⁺=357.1.

[1584] Preparation 17

[1585] 3-[(Dipropylamino)carbonyl]-5-[(methylamino)-sulfonyl]BenzoicAcid (XXXIX)

[1586] Following the general procedure of PREPARATION 13 and makingnon-critical variations, the title compound is obtained, MS (ESI+) forC₁₅H₂₂N₂O₅S m/z (M+H)⁺=343. 1.

[1587] Preparation 18

[1588] Methyl3-[(dimethylamino)sulfonyl]-5-[(dipropylamino)-carbonyl]Benzoate(XXXVIII)

[1589] Following the general procedure of PREPARATION 12 and makingnon-critical variations but using dimethylamine (2 N solution in THF,0.692 mL, 1.38 mmol), the title compound is obtained, MS (ESI+) forC₁₇H₂₆N₂O₅S m/z (M+H)₊=371.1.

[1590] Preparation 19

[1591] 3-[(Diimethylamino)sulfonyl]-5-[(dipropylamino)carbonyl]-BenzoicAcid (XXXIX)

[1592] Following the general procedure of PREPARATION 13 and makingnon-critical variations, the title compound is obtained, MS (ESI+) forC₁₆H₂₄N₂O₅S m/z (M+H)⁺=357.1.

[1593] Preparation 20

[1594] Methyl ³-[(dipropylamino)carbonyl]-5-Ethylbenzoate (IX)

[1595] Ethylboronic acid (0.800 g, 10.8 mmol),dichlorobis(triphenylphosphine)-palladium(II) (0.252 g, 0.360 mmol),potassium carbonate (2.50 g, 18.0 mmol) and lithium chloride (0.151 g,3.60 mmol) are added to a mixture of methyl3-bromo-5-[(dipropylamino)carbonyl]benzoate (1.23 g, 3.60 mmol) in dryDMF (20 mL). The mixture is heated at 100 degrees C. for 18 hours. Themixture is then partitioned between ethyl acetate and water. The phasesare separated and the ethyl acetate phase is washed with saline, driedover sodium sulfate and concentrated. The concentrate is columnchromatographed (silica gel; ethyl acetate/hexanes, 15/85) to give thetitle compound, MS (ESI+) for C₁₇H2₅NO₃ m/z (M+H)⁺=292.2.

[1596] Preparation 21

[1597] 3-[(Dipropylamino)carbonyl]-5-Ethylbenzoic Acid (IX)

[1598] Lithium hydroxide monohydrate (0.0680 g, 1.6 mmol) is added to amixture of methyl 3-[(dipropylamino)carbonyl]-5-ethylbenzoate(PREPARATION 20, 0.450 g, 1.6 mmol) in a mixture of THF/methanol/water(2/1/1, 8 mL). The mixture is stirred at 20-25 degrees C. for 3 hours.The mixture is then diluted with water (20 mL) and hydrochloric acid (1N) is added to bring the pH to less than 3. The aqueous mixture isextracted with ethyl acetate. The organic phase is separated and washedwith saline, dried over anhydrous magnesium sulfate, filtered andconcentrated to give the title compound, MS (ESI+) for C₁₆H₂₃NO₃ m/z(M+H)⁺=278.2.

Example 1 tert-Butyl(1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate (III)

[1599] N-methyl-morpholine (5.83 Ml, 53 mmole, 1.05 eq.) is added to(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid(II, 15 g, 50 mmole) in THF (100 mL) and the reaction is cooled to −78degrees C. Isobutyl chloroformate (6.87 mL, 53 mmole, 1.05 eq.) is addedrapidly. The cold bath is then removed and the mixture stirred for 1hour. The reaction is monitored by TLC to insure completion of thereaction and the mixture is then filtered and washed with dry THF (50ml) and kept cold in the filtered flask at −20 degrees C.

[1600] In an ice-salt bath is placed a 500 ml graduate cylindercontaining ether (200 mL) and aqueous potassium hydroxide (40%, 60 ml).1-Methyl-3-nitro-1-nitrosoguanidine (5.6 g, 106 mmole, 2.1 eq.) is addedslowly with stirring and temperature kept below 0 degrees C. The mixtureturned yellow and the bubbling lasted for 10 minutes. The stirring isstopped and without mixing the layers, the top diazomethane ethereallayer is transferred with non-ground tip pipette into the stirred mixedanhydride mixture at −20 degrees C. The reaction is monitored by TLC(ethyl acetate/hexane, 50/50; R_(f)=0.69). After 1 hour nitrogen is thenbubbled into the mixture. The solvent is removed under reduced pressure(with heat) and the mixture is partitioned between ether and water. Thephases are separated, the organic phase is washed with bicarbonate,saline, dried over anhydrous sodium sulfate and solvent removed underreduced pressure (with heat). The residue is dissolved in ether (100 mL)and hydrobromic acid (48%, 15 mL, 135 mmole, 2.7 eq,) is added at −20degrees C., the cold bath is removed and the mixture is stirred foranother 0.5 hours. The reaction is monitored by TLC (ethylacetate/hexane, 50/50; R_(f)=0.88). The mixture is partitioned betweenether and water, washed with bicarbonate, saline, dried over anhydroussodium sulfate and the solvent removed. The residue is recrystallizedfrom ethanol to give the title compound, TLC (ethyl acetate/hexane,50/50) R_(f)=0.88; MS (MH+)=379.3.

Example 2 tert-Butyl(1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (IV)

[1601] Sodium borohydride (1.32 g, 34.9 mmole, 1.1 eq.) is added totert-Butyl (1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate(III, EXAMPLE 1, 12 g, 31.75 mmole) dissolved in absolute alcohol (500mL) at −78 degrees C. The reaction mixture is stirred for 0.5 hour andmonitored by TLC (ethyl acetatethexane, 20/80; R_(f)=0.2). The mixtureis quenched with water (10 mL) and the solvent removed under reducedpressure with heat (not exceeding 30 degrees C.) to dryness. The solidis partitioned between dichloromethane and water, washed with saline,dried over anhydrous sodium sulfate. The solvent is removed underreduced pressure to give the title compound, TLC (ethyl acetate/hexane,20/80) R_(f)=0.2; MS (MH+)=381.2.

Example 3 tert-Butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V)

[1602] tert-Butyl(1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (IV,EXAMPLE 2) is dissolved in absolute alcohol (150 mL) and ethyl acetate(100 mL) and potassium hydroxide (2.3 g, 34.9 mmole, 1.1 eq.) in ethylalcohol (85%, 5 mL) is added at −20 degrees C. The cold bath is thenremoved and the mixture stirred for 0.5 hour. The reaction is monitoredby TLC (ethyl acetate/hexane, 20/80). When the reaction is complete, itis diluted with dichloromethane and extracted, washed with water,saline, dried over anhydrous sodium sulfate and the solvent removedunder reduced pressure. The crude material is purified by flashchromatography on silica gel to give the title compound, TLC (ethylacetate/hexane, 20/80) R_(f)=0.3; MS (MH+)=300.4.

Example 4 tert-Butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII)

[1603] tert-Butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3, 245 mg, 0.82 mmol) is suspended in isopropyl alcohol (6 mL) and3-methoxybenzylamine (160 microL, 1.22 mmol) is added with stirring at20-25 degrees C. This mixture is heated to gentle reflux (bath temp 85degrees C.) under nitrogen for 2 hours, whereupon the resulting mixtureis concentrated under reduced pressure to give the title compound. Thetitle compound is purified by flash chromatography (2-5%methanol/methylene chloride; gradient elution) to give purified titlecompound.

Example 5(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanolTrifluoroacetate (VIII)

[1604] tert-Butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII, EXAMPLE 4, 258 mg, 0.59 mmol) is dissolved in methylene chloride(1 mL) at 20-25 degrees C., and trifluoroacetic acid (1 mL) is addedwith stirring under nitrogen. The reaction mixture is stirred at 20-25degrees C. for 1 hour, whereupon the reaction mixture is concentratedunder reduced pressure to give the title compound. The title compound isused in the next reaction without further purification.

Example 6N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1605](2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoltrifluoroacetate salt (VIII, EXAMPLE 5) is dissolved in anhydrous DMF (3mL) and cooled to 0 degrees C. Triethylamine (500 microliter, 3.6 mmol)and 5-methyl-N, N-dipropylisophthalamic acid (156 mg, 0.59 mmol) areadded with stirring. The mixture is warmed to 20-25 degrees C. brieflyto allow for complete dissolution of the carboxylic acid, beforerecooling to 0 degrees C. 1-Hydroxybenzotriazole (157 mg, 1.2 mmol) isadded with stirring, followed by1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (229 mg, 1.2mmol). The resulting mixture is stirred at 0 degrees C. for 5 minutes,then warmed to 20-25 degrees C. for 15 hours. The reaction mixture isthen quenched with aqueous citric acid (10%), and the mixture extractedthree times with ethyl acetate. The combined organic extracts are washedwith saturated sodium bicarbonate, saline, dried over sodium sulfate,filtered and concentrated under reduced pressure to give the the titlecompound in crude form. This material is purified by flashchromatography (2-10% methanol/methylene chloride gradient elution) togive purified title compound, MS (ES) MH⁺=582.3.

Examples 7-9

[1606] Following the general procedure of EXAMPLE 1 and making noncritical variations but starting with the protecting group of Column Aand using the acid of Column B, the protected compound (III) of Column Cis obtained: EXAMPLE Column A Column B Column C 7 BOC Hydrochlorictert-butyl(1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate 8CBZ Hydrobromicbenzyl(1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate 9 CBZHydrochloricbenzyl(1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

Examples 10-12

[1607] Following the general procedure of EXAMPLE 2 and making noncritical variations but starting with the protected compound (III) ofColumn A, the alcohol (IV) of Column B is obtained: EXAMPLE Column AColumn B 10 7 Tert-butyl(1S,2S)-3-chloro-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate 11 8Benzyl(1S, 2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate12 9 Benzyl(1S,2S)-3-chloro-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate

Example 13 Benzyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V)

[1608] Following the general procedure of EXAMPLE 3 and making noncritical variations but starting with the alcohol (IV) of EXAMPLE 12,the title compound is obtained.

Examples 14-107

[1609] Following the general procedure of EXAMPLE 4 and makingnon-critical variations but reacting tert-butyl(1S,2S)-1-(2-oxiranyl)-2-phenylethylcarbamate (V, commerciallyavailable) with the C-terminal amine (VI) of Column A, the protectedalcohol (VII) of Column B is obtained. Column A Column B EXA C-terminalamine (VI) Protected alcohol (VII) 14 H₂N—CH₂CH₃ tert-butyl(1S,2R)-1-benzyl-3-(ethylamino)-2-hydroxypropylcarbamate 15 H₂N—CH₂-phenyltert-butyl(1S, 2R)-1-benzyl-3-(benzylamino)-2-hydroxypropylcarbamate 16H₂N—CH(CH₃)₂ tert-butyl(1S,2R)-1-benzyl-3-(isoproylamino)-2-hydroxypropylcarbamate 17H₂N—CH₂-phenyl-4-CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methylbenzyl)amino]propylcarbamate 18H₂N—(CH₂)₂-phenyl-4-OCH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methoxyphenyl)ethyl]amino}propylcarbamate19 H₂N—CH₂-phenyl-3-OCH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]proylcarbamate 20H₂N—CH(-phenyl)-CO—OC₂H₅ ethyl({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}amino)(phenyl)ace-tate 21 H₂N—(CH₂)₂phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylethyl)amino]propylcarbamate 22H₂N—CH(—CH₂OH)—CH(OH)-phenyl-4-NO₂ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-(hydroxymethyl)-2-(4-nitro-phenyl)ethyl]amino}propylcarbamate 23 H₂N—CH₂-phenyl-2-Cl tert-butyl(1S,2R)-1-benzyl-3-[(2-chlorobenzyl)amino]-2-hydroxypropylcarbamate 24H₂N—CH₂-phenyl-4-Cl tert-butyl(1S,2R)-1-benzyl-3-[(4-chlorobenzyl)amino]-2-hydroxypropylcarbamate 25H₂N—(CH₂)₂—O—(CH₂)₂—OH tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-hydroxyethoxy)ethyl]amino}propylcarbamate26 H₂N-1-indanyl tert-butyl(1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-1-ylamino)-2-hydroxypropylcarbamate27 H₂N—CH₂—CH(OH)—CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxypropyl)amino]propylcarbamate 28H₂N—CH₂-tetrahydrofuranyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(tetrahydro-2-furanylmethyl)amino]propylcarbamate29 H₂N—CH₂—CH(—OCH₂CH₃) tert-butyl(1S,2R)-1-benzyl-3-[(2,2-diethoxyethyl)amino]-2-hydroxypropylcarbamate 30H₂N—(CH₂)₄—CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-(pentylamino)propylcarbamate 31 H₂N-cyclohexyltert-butyl(1S, 2R)-1-benzyl-3-(cyclohexylamino)-2-hydroxypropylcarbamate32 H₂N—CH₂-pyridin-2-yl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-pyridinylmethyl)amino]propylcarbamate 33H₂N—CH₂-phenyl-2-NH₂ tert-butyl(1S,2R)-3-[(2-aminobenzyl)amino]-1-benzyl-2-hydroxypropylcarbamate 34H₂N—CH₂-pyridin-3-yl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-pyridinylmethyl)amino]propylcarbamate 35H₂N—(CH₂)₂-pyrrolidin-1-yl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-pyrrolidinyl)ethyl]amino}propylcarbamate36 H₂N—CH₂—CH(OH)-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propylcarbamate37 H₂N—(CH₂)₃—O—(CH₂)₃—CH₃ tert-butyl(1S,2R)-1-benzyl-3-[(3-butoxypropyl)amino]-2-hydroxypropylcarbamate 38H₂N—(CH₂)₃—O—CH(CH₃)₂ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-isopropoxypropyl)amino]propylcarbamate 39H₂N—(CH₂)₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propylcarbamate 40H₂N—(CH₂)₃-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-phenylpropyl)amino]propylcarbamate 41H₂N—(CH₂)₂—OCH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-methoxyethyl)amino]propylcarbamate 42H₂N—(CH₂)₂—O-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenoxyethyl)amino]propylcarbamate 43H₂N—(CH₂)₂—O—(CH₂)₂—CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-propoxyethyl)amino]propylcarbamate 44H₂N—(CH₂)₂—C(CH₃)₃ tert-butyl(1S,2R)-1-benzyl-3-[(3,3-dimethylbutyl)amino]-2-hydroxypropylcarbamate 45H₂N—(CH₂)₄-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-phentylbutyl)amino]propylcarbamate 46H₂N—CH₂-phenyl-3-I tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propylcarbamate 47H₂N—CH₂-phenyl-4-NO₂ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-nitrobenzyl)amino]propylcarbamate 48H₂N—CH₂-phenyl-3-Cl tert-butyl(1S,2R)-1-benzyl-3-[(3-chlorobenzyl)amino]-2-hydroxypropylcarbamate 49H₂N—(CH₂)₂-phenyl-4-Cl tert-butyl(1S,2R)-1-benzyl-3-{[2-(4-chlorophenyl)ethyl]amino}-2-hydroxypropylcarbamate50 H₂N—(CH₂)₂-pyridin-2-yl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-pyridinyl)ethyl]amino}propylcarbamate 51H₂N—CH₂-pyridin-4-yl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-pyridinylmethyl)amino]propylcarbamate 52H₂N—(CH₂)₂—(N-methylpyrrolidin-2-yl) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}propyl-carbamate 53 H₂N—CH₂-phenyl-2,3-dimethyl tert-butyl(1S,2R)-1-benzyl-3-[(2,3-dimethylbenzyl)amino]-2-hydroxypropylcarbamate 54H₂N—CH₂-phenyl-2-OCF₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethoxy)benzyl]amino}propyl-carbamate 55 H₂N—CH₂-phenyl-2-Cl-6-O-phenyl tert-butyl(1S,2R)-1-benzyl-3-[(2-chloro-6-phenoxybenzyl)amino]-2-hydroxypropylcarbamate56 H₂N—CH₂-phenyl-4-CF₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethyl)benzyl]amino}propylcarbamate57 H₂N—CH₂-phenyl-2,3-dichloro tert-butyl(1S,2R)-1-benzyl-3-[(2,3-dichlorobenzyl)amino]-2-hydroxypropylcarbamate 58H₂N—CH₂-phenyl-3,5-dichloro tert-butyl(1S,2R)-1-benzyl-3-[(3,5-dichlorobenzyl)amino]-2-hydroxypropylcarbamate 59H₂n—CH₂-phenyl-3,5-difluoro tert-butyl(1S,2R)-1-benzyl-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropylcarbamate 60H₂N—CH₂-phenyl-4-OCF₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethoxy)benzyl]amino}propyl-carbamate 61 H₂N—(CH₂)₂-phenyl-4-SO₂—NH₂ tert-butyl(1S,2R)-3-{[4-(aminosulfonyl)benzyl]amino}-1-benzyl-2-hydroxypropylcarbamate62 H₂N—CH₂-phenyl-4-OCH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methoxybenzyl)amino]propylcarbamate 63H₂N—CH₂-phenyl-4-CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methylbenzyl)amino]propylcarbamate 64H₂N—CH₂—Ph-(3,4,5-trimethoxy) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3,4,5-trimethoxybenzyl)amino]propylcarbamate65 H₂N—CH₂-phenyl-3-OCF₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl-carbamate 66 H₂—CH₂-phenyl-3,5-dimethoxy tert-butyl(1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropylcarbamate 67H₂N—CH₂-phenyl-2,4-dimethoxy tert-butyl(1S,2R)-1-benzyl-3-[(2,4-dimethoxybenzyl)amino]-2-hydroxypropylcarbamate 68H₂N—CH₂-phenyl-phenyl tert-butyl(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-2-hydroxypropylcarbamate69 H₂N—CH₂-phenyl-3,4-dichloro tert-butyl(1S,2R)-1-benzyl-3-[(3,4-dichlorobenzyl)amino]-2-hydroxypropycarbamate 70H₂N—CH₂-phenyl-4-F tert-butyl(1S,2R)-1-benzyl-3-[(4-fluorobenzyl)amino]-2-hydroxypropylcarbamate 71H₂N—CH₂-phenyl-3-CF₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propylcarbamate72 H₂N—CH₂-phenyl-2-CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-methylbenzyl)amino]propylcarbamate 73H₂N—CH(R)—CH₃)-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-phenylethyl]amino}propylcarbamate 74H₂N—CH((S)—CH₃)-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-phenylethyl]amino}propylcarbamate 75H₂N—CH₂-phenyl-3,5-(bis)trifluoromethyl tert-butyl(1S,2R)-1-benzyl-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-2-hydroxy-propylcarbamate 76 H₂N—CH₂-phenyl-2-CF₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethyl)benzyl]amino}propylcarbamate77 H₂N—CH((S)—CH₃)-(naphth-1-yl) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-(1-naphthyl)ethyl]amino}propylcarbamate78 —NH₂—CH(R)—CH₃)-(naphth-1-yl) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-(1-naphthyl)ethyl]amino}propylcarbamate79 H₂N—CH₂-phenyl-3-OCH₃-4-OH tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxy-3-methoxybenzyl)amino]propyl-carbamate 80 H₂N—CH₂-phenyl-3,4-dihydroxy tert-butyl(1S,2R)-1-benzyl-3-[(3,4-dihydroxybenzyl)amino]-2-hydroxypropylcarbamate 81H₂N—(CH₂)₃—OCH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino]propylcarbamate 82H₂N—CH((S)—CH₃)—CH₂—OH tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-methylethyl]amino}propyl-carbamate 83 H₂N—CH((R)—CH₃)—CH₂—OH tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-methylethyl]amino}propyl-carbamate 84 H₂N—CH₂—C≡CH tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-(2-propynylamino)propylcarbamate 85H₂N—(CH₂)₂-phenyl-2-F tert-butyl(1S,2R)-1-benzyl-3-{[2-(2-fluorophenyl)ethyl]amino}-2-hydroxypropylcarbamate86 H₂N—(CH₂)₂-phenyl-3-F tert-butyl(1S,2R)-1-benzyl-3-{[2-(3-fluorophenyl)ethyl]amino}-2-hydroxypropylcarbamate87 H₂N—(CH₂)₂-phenyl-4-F tert-butyl(1S,2R)-1-benzyl-3-{[2-(4-fluorophenyl)ethyl]amino}-2-hydroxypropylcarbamate88 H₂N—(CH₂)₂-phenyl-4-Br tert-butyl(1S,2R)-1-benzyl-3-{[2-(4-bromophenyl)ethyl]amino}-2-hydroxypropylcarbamate89 H₂N—(CH₂)₂-phenyl-3-OCH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(3-methoxyphenyl)ethyl]amino}propylcarbamate90 H₂N—(CH₂)₂-phenyl-2,4-dichloro tert-butyl(1S,2R)-1-benzyl-3-{[2-(2,4-dichlorophenyl)ethyl]amino}-2-hydroxy-propylcarbamate 91 H₂N—(CH₂)₂-phenyl-3-Cl tert-butyl(1S,2R)-1-benzyl-3-{[2-(3-chlorophenyl)ethyl]amino}-2-hydroxypropylcarbamate92 H₂N—(CH₂)₂-phenyl-2,5-dimethoxy tert-butyl(1S,2R)-1-benzyl-3-{[2-(2,5-dimethoxyphenyl)ethyl]amino}-2-hydroxy-propylcarbamate 93 H₂N—(CH₂)₂-phenyl-4-CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methylphenyl)ethyl]amino}propylcarbamate94 H₂N—CH(—(R)CH₂—OH)—CH₂-phenyl tert-butyl(1S,2R)-1-benzyl-3-{[(1R)-1-benzyl-2-hydroxyethyl]amino}-2-hydroxy-propylcarbamate 95 H₂N—(CH₂)₃-(1-morpholinyl) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-morpholinyl)propyl]amino}propylcarbamate96 H₂N—CH₂—C(CH₃)₂ tert-butyl(1S,2R)-1-benzyl-3-[(3,3-dimethylbutyl)amino]-2-hydroxypropylcarbamate 97H₂N—(CH₂)₂-(1-morpholinyl) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-morpholinyl)ethyl]amino}propylcarbamate98 H₂N—CH(OH)—CH₂—CH₃ tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(1-hydroxypropyl)amino]propylcarbamate 99H₂N—(CH₂)₂-(thien-2-yl) tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(2-thienylmethyl)amino]propylcarbamate 100H₂N—(CH₂)₄—OH tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxybutyl)amino]propylcarbamate 101H₂N—CH(—(S)CH₂—OH)-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-phenylethyl]amino}propyl-carbamate 102 H₂N—CH₂-phenyl-2,4-dichloro tert-butyl(1S,2R)-1-benzyl-3-[(2,4-dichlorobenzyl)amino]-2-hydroxypropylcarbamate 103H₂N—CH(—(R)CH₂—OH)-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-phenylethyl]amino}propyl-carbamate 104 H₂N—CH₂-phenyl-4-C(CH₃)₃ tert-butyl(1S,2R)-1-benzyl-3-[(4-tert-butylbenzyl)amino]-2-hydroxypropylcarbamate 105H₂N—CH(CH₃)-phenyl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[(1-phenylethyl)amino]propylcarbamate 106H₂N-(1R, 2S)-2-hydroxyinden-1-yl tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]a- mino}propylcarbamate 107H₂N—CH₂-phenyl-3,4-dimethyl tert-butyl(1S,2R)-1-benzyl-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropylcarbamate

Examples 108-164

[1610] Following the general procedure of EXAMPLE 4 and makingnon-critical variations but reacting tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3) with the C-terminal amine (VI) of Column A, the protected alcohol(VII) of Column B is obtained. Column A Column B EXA C-terminal amin(VI) Protected alcohol (VII) 108 H₂N—(CH₂)₆—CO—O—CH₃ methyl 7-{[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-(3,5-difluoro-phenyl)-2-hydroxybutyl]amino}heptanoate 109H₂N—CH(—CH₃)—CO—NH—CH₂—CH(CH₃)₂ r/s tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutyl-amino)-1-methyl-2-oxoethyl]amino}propylcarbamate 110H₂N—CH((S)—CH₃)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(iso-butylamino)-1-methyl-2-oxoethyl]amino}propylcarbamate 111H₂N—C(—CH₃)₂—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutyl-amino)-1,1-dimethyl-2-oxoethyl]amino}propylcarbamate 112H₂N—CH₂—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutyl-amino)-2-oxoethyl]amino}propylcarbamate 113H₂N—CH((S)—CH₂CH₃)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(iso-butylamino)carbonyl]propyl}amino)propylcarbamate 114H₂N—CH((R)—CH₂CH₃)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(iso-butylamino)carbonyl]propyl}amino)propylcarbamate 115 H₂N—CH₂-phenyltert-butyl(1S, 2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxy-propylcarbamate 116 H₂N—CH₂—CH₃ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-(ethyl- amino)-2-ydroxypropylcarbamate 117H₂N—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isobutyl- amino)propylcarbamate118 H₂N—CH₂—CH(CH₃)—CONH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isobutyl-amino)-2-methyl-3-oxopropyl]amino}propylcarbamate 119H₂N—CH₂-phenyl-4-N(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[4-(dimethyl-amino)benzyl]amino}-2-hydroxypropylcarbamate 120H₂N—CH((S)—CH₂-phenyl)-CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-3-{[(1S)-1-(3,5-difluorobenzyl)-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate 121H₂N—CH((S)—CH(CH₃)₂)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(iso-butylamino)carbonyl]-3-methylbutyl}amino)propylcarbamate 122H₂N—CH₂—CH₂—N(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[2-(dimethyl-amino)ethyl]amino}-2-hydroxypropylcarbamate 123 H₂N—CH₂-(pyridin-3-yl)tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-pyridinyl-methyl)amino]propylcarbamate 124H₂N—CH((S)—CH₂—O—CH₂-phenyl)-CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-3-{[(1S)-1-[(benzyloxy)methyl]-2-(isobutyl-amino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hdyroxy-propylcarbamate 125 H₂N—C(—CH₃)₂-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-meth-yl-1-phenylethyl)amino]propylcarbamate 126H₂N—CH((R)—CH(CH₃)₂)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(iso-butylamino)carbonyl]-3-methylbutyl}amino)propylcarbamate 127H₂N—CH((S)—CH₂—CH₂—CH₃)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(iso-butylamino)carbonyl]butyl}amino)propylcarbamate 128H₂N—CH((S)—CH₂—OH)—CO—NH—CH₂—CH(CH₃)₂ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-1-(hy-droxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propylcarbamate 129H₂N—CH₂—CH₂-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenyl-ethyl)amino]propylcarbamate 130 H₂N—CH((S)—CH₃)—CO—NH—CH₂-phenyltert-butyl(1S, 2R)-3-{[2-(benzylamino)-1-methyl-2-ox-oethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate 131H₂N—CH((S)—CH₂—CH₃)-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1S)-2-(benzyl-amino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropylcarbamate 132H₂N—CH₂-phenyl-3-OCH₃ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxy-benzyl)amino]propylcarbamate 133 H₂N—CH((S)-phenyl)CO—NHCH₂CH(CH₃)₂tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(iso-butylamino)-2-oxo-1-phenylethyl]amino}propylcarbamate 134H₂N—CH₂—CH₂—CH(CH₃)₂ tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hy-droxy-3-(isopentylamino)propylcarbamate 135 H₂N-cyclohexyltert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-3-(cyclohexylamino)-2-hy-droxypropylcarbamate 136 H₂N—(CH₂)₃—CH₃ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-(butylamino)-2-hydroxy- propylcarbamate 137H₂N—(CH₂)₃-O—CH₃ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxy-propyl)amino]propylcarbamate 138 H₂N—CH₂—CH(OH)-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hy-droxy-2-phenylethyl)amino]propylcarbamate 139H₂N-cyclohexyl-3,5-dimethoxy tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3R, 5S)-3,5-dimethoxy-cyclohexyl]amino}-2-hydroxypropylcarbamate 140H₂N-cyclohexyl-3,5-di-(—CO—OCH₃) dimethyl(1R, 3S)-5-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hy-droxy-4-phenylbutyl}amino)-1,3-cyclohexanedicarboxylate 141H₂N-cyclohexyl-3,5-di-(—COOH) (1R, 3S)-5-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hy-droxy-4-phenylbutyl}amino)-1,3-cyclohexanedicarboxylic acid 142H₂N—CH(R)—CH₂—CH₃)-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-1-phenyl-propyl]amino}propylcarbamate 143 H₂N—CH₂-phenyl-3-Cl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-chloro-benzyl)amino]-2-hydroxypropylcarbamate 144 H₂N—CH₂-phenyl-3-OCH₃tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxy-benzyl)amino]propylcarbamate 145 H₂N—CH₂-phenyl-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-[((1,1′-biphenyl]-3-ylmeth-yl)amino]-2-hydroxypropylcarbamate 146 H₂N—CH₂-phenyl-3-I tert-butyl(1S,2R)-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodo-benzyl)amino]propylcarbamate 147 H₂N—CH₂-phenyl-3-CH₃ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methyl-benzyl)amino]propylcarbamate 148 H₂N—CH₂—CH(—CH₃)-phenyl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenyl-propyl)amino]propylcarbamate 149 H₂N—CH₂-(thiazol-5-yl) tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thia-zol-5-ylmethyl)amino]propylcarbamate 150 H₂N—CH₂-(thien-2-yl)tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-thienyl-methyl)amino]propylcarbamate 151 H₂N-4-methoxytetralin-1-yltert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-meth-oxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propylcarbamate 152H₂N—CH₂-pyrazin-2-yl tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyrazinyl-methyl)amino]propylcarbamate 153 H₂N—CH₂-phenyl-3,5-difluorotert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-3-[(3,5-difluoro-benzyl)amino]-2-hydroxypropylcarbamate 154H₂N—CH₂-phenyl-3,4-methylenedioxy tert-butyl(1S,2R)-3-[(1,3-benzodioxol-5-ylmethyl)amino]-1-(3,5-di-fluorobenzyl)-2-hydroxypropylcarbamate 155 H₂N—CH₂-phenyl-3,5-dimethoxytert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethoxy-benzyl)amino]-2-hydroxypropylcarbamate 156 H₂N—CH₂-phenyl-3-CF₃tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoro-methyl)benzyl]amino}propylcarbamate 157 H₂N—CH₂-(furan-2-yl)tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)a-mino]-2-hydroxypropylcarbamate 158 H₂N-(7-methoxytetralin-1-yl)tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-meth-oxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propylcarbamate 159H₂N—CH₂-phenyl-3-O—CF₃ tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoro-methoxy)benzyl]amino}propylcarbamate 160 H₂N—CH₂-phenyl-3-Ftert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-3-[(3-fluoro-benzyl)amino]-2-hydroxypropylcarbamate 161 H₂N—CH₂-phenyl-3-O—CH(CH₃)₂tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iso-propoxybenzyl)amino]propylcarbamate 162 H₂N—CH₂-phenyl-3-Brtert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-3-[(3-bromo-benzyl)amino]-2-hydroxypropylcarbamate 163 H₂N—CH₂-(5-methylfuran-2-yl)tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-meth-yl-2-furyl)methyl]amino}propylcarbamate 164 H₂N-(5-methoxytetralin-1-yl)tert-butyl(1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-meth-oxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propylcarbamate

Example 165tert-Butyl-(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate(XII)

[1611] Sodium azide (0.22 g, 4 mmole) and ammonium chloride (2 eq) areadded to tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3, 0.6 g, 2 mmole). The reaction is heated to 75-80 degrees C. andstirred for 16 hours. The reaction is monitored by TLC to insurecompletion. The solvent is removed under reduced pressure. Theconcentrate is partitioned between ethyl acetate and water, the phasesare separated and the organic phase is washed with bicarbonate andsaline, dried over anhydrous sodium sulfate and concentrated to give thetitle compound, TLC (ethyl acetate/hexane) R_(f)=0.45; MS (MH⁺)=343.

Example 166 (2R,3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-butanol(XIV)

[1612]tert-Butyl-(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate(XII, EXAMPLE 165, 0.48 g, 1.41 mmole) is dissolved in dichloromethane(20 ml) to which trifluoroacetic acid (5 ml) is added. The reaction isstirred at 20-25 degrees C. for 16 hours and the solvent is removedunder reduced pressure with heat. Ethyl acetate is added twice andevaporated twice to give the title compound as the trifluoroacetic acidsalt which is used in the next reaction without further purification; MS(MH⁺)=242.

Example 167N¹-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N³,N³-dipropylisophthalamide(XV)

[1613] To (2R,3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-buta (XIV,EXAMPLE 166, 0.34 g, 1.4 mmole) in dichloromethane (20 ml) is addedN,N-dipropylamidoisophthalic acid (IX, 0.53 g, 2 mmole), t-butyl alcohol(0.27 g, 2 mmole) and triethylamine (0.84 ml, 6 mmole) andethyl-1-(3-dimethylaminopropyl)carbodiimide (0.58 g, 3 mmole). Themixture is stirred at 20-25 degrees C. for 16 hours. The reaction ismonitored by TLC (methanol/dichloromethane, 20/80+ethyl acetate/hexane,50/50; R_(f)=0.76). When the reaction is complete as measured by TLC,the reaction mixture is partitioned between dichloromethane and water,washed with hydrochloric acid (0.5 N), bicarbonate, saline, dried overanhydrous sodium sulfate and the solvent is removed under reducedpressure with heat to produce a concentrate. The concentrate is columnchouromatographed on silica gel to give the title compound; MS(MH⁺)=488.

Example 168N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamideAcetic Acid Salt (XVI)

[1614]N¹-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N³,N³-dipropylisophthalamide(XV, EXAMPLE 167, 0.3 g, 0.62 mmole) in ethyl acetate (20 ml) and aceticacid (5 ml) is placed in a Parr pressure bottle. Palladium on carbon(10%, 5 g) is added and the mixture shaken under hydrogen at 50 psi for2 hours. The mixture is filtered through a diatomaceous earth and thefiltrate is concentrated to give the title compound; MS (MH⁺)=462.

Example 169N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1615]N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamideacetic acid salt (XVI, EXAMPLE 168, 76 mg, 0.146 mmol) is dissolved inabsolute ethanol (2 mL). 3-Furaldehyde (20 microL, 0.231 mmol) andtriethylamine (30 microL, 0.215 mmol) are added via syringe, withstirring at 20-25 degrees C. After 10 minutes, palladium on carbon 122mg, 5 weight %) is added and the mixture placed under a hydrogenatmosphere (50 psi) and shaken for 20 minutes. The resulting mixture isthen filtered through diatomaceous earth, with ethanol washings. Thefiltrate is purified by flash chromatography (2-10% methanol/methylenechloride) to give purified title compound, MS (MH⁺)=542.2.

Example 169a tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1S)-2-(ethylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropylcarbamate(VII)

[1616] Following the general procedure of EXAMPLEs 4 and 14-164 andmaking non-critical variations and reacting tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3) with (2S)-2-amino-N-ethylpropanamide (VI), the title compound isobtained.

Examples 170-320

[1617] Following the general procedure of EXAMPLE 5 and makingnon-critical variations but starting with the protected alcohol (VII) ofColumn A, the amine (VIII) of Column B is obtained. Column A ProtectedAlcohol (VII) Compound of Column B EXA EXAMPLE Amine (VIII) 170 14 (2R,3S)-3-amino-1-(ethylamino)-4-phenyl-2-butanol 171 15 (2R,3S)-3-amino-1-(benzylamino)-4-phenyl-2-butanol 172 16 (2R,3S)-3-amino-1-(isopropylamino)-4-phenyl-2-butanol 173 17 (2R,3S)-3-amino-1-[(4-methylbenzyl)amino]-4-phenyl-2-butanol 174 18 (2R,3S)-3-amino-1-{[2-(4-methoxyphenyl)ethyl]amino}-4-phenyl-2-butanol 17519 (2R, 3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol 176 20ethyl{[(2R, 3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}(phenyl)acetate177 21 (2R, 3S)-3-amino-4-phenyl-1-[(2-phenylethyl)amino]-2-butanol 17822 (2S)-2-{[2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}-1-(4-nitorphenyl)-1,3-propanediol179 23 (2R, 3S)-3-amino-1-[(2-chlorobenzyl)amino]-4-phenyl-2-butanol 18024 (2R, 3S)-3-amino-1-[(4-chlorobenzyl)amino]-4-phenyl-2-butanol 181 25(2R, 3S)-3-amino-1-{[2-(2-hydroxyethoxy)ethyl]amino}-4-phenyl-2-butanol182 26 (2R,3S)-3-amino-1-(2,3-dihydro-1H-inden-1-ylamino)-4-phenyl-2-butanol 183 27(2R, 3S)-3-amino-1-[(2-hydroxypropyl)amino]-4-phenyl-2-butanol 184 28(2R, 3S)-3-amino-4-phenyl-1-[(tetrahydr-2-furanylmethyl)amino]-2-butanol185 29 (2R, 3S)-3-amino-1-[(2,2-diethoxyethyl)amino]-4-phenyl-2-butanol186 30 (2R, 3S)-3-amino-1-(butylamino)-4-phenyl-2-butanol 187 31 (2R,3S)-3-amino-1-(cyclohexylamino-4-phenyl-2-butanol 188 32 (2R,3S)-3-amino-4-phenyl-1-[2-pyridinylmethyl)amino]-2-butanol 189 33 (2R,3S)-3-amino-1-[(2-aminobenzyl)amino]-4-phenyl-2-butanol 190 34 (2R,3S)-3-amino-4-phenyl-1-[(3-pyridinylmethyl)amino]-2-butanol 191 35 (2R,3S)-3-amino-4-phenyl-1-{[2-(1-pyrrolidinyl)ethyl]amino}-2-butanol 192 36(2R, 3S)-3-amino-1-[(2-hydroxy-2-phenylethyl)amino]-4-phenyl-2-butanol193 37 (2R, 3S)-3-amino-1-[(3-butoxypropyl)amino]-4-phenyl-2-butanol 19438 (2R, 3S)-3-amino-1-[(3-isopropoxypropyl)amino]-4-phenyl-2-butanol 19539 (2R, 3S)-3-amino-1-(isopentylamino)-4-phenyl-2-butanol 196 40 (2R,3S)-3-amino-4-phenyl-1-[(3-phenylpropyl)amino]-2-butanol 197 41 (2R,3S)-3-amino-1-[(2-methoxyethyl)amino]-4-phenyl-2-butanol 198 42 (2R,3S)-3-amino-1-[(2-phenoxyethyl)amino]-4-phenyl-2-butanol 199 43 (2R,3S)-3-amino-4-phenyl-1-[(2-propoxyethyl)amino]-2-butanol 200 44 (2R,3S)-3-amino-1-[(3,3-dimethylbutyl)amino]-4-phenyl-2-butanol 201 45 (2R,3S)-3-amino-4-phenyl-1-[(4-phenylbutyl)amino]-2-butanol 202 46 (2R,3S)-3-amino-1-[(3-iodobenzyl)amino]-4-phenyl-2-butanol 203 47 (2R,3S)-3-amino-1-[(4-nitrobenzyl)amino]-4-phenyl-2-butanol 204 48 (2R,3S)-3-amino-1-[(3-chlorobenzyl)amino]-4-phenyl-2-butanol 205 49 (2R,3S)-3-amino-1-{[2-(4-chlorophenyl)ethyl]amino}-4-phenyl-2-butanol 206 50(2R, 3S)-3-amino-4-phenyl-1-{[2-(2-pyridinyl)ethyl]amino}-2-butanol 20751 (2R, 3S)-3-amino-4-phenyl-1-[(4-pyidinylmethyl)amino]-2-butanol 20852 (2R,3S)-3-amino-1-{[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}-4-phenyl-2-butanol209 53 (2R, 3S)-3-amino-1-[(2,3-dimethylbenzyl)amino]-4-phenyl-2-butanol210 54 (2R,3S)-3-amino-4-phenyl-1-{[2-(trifluoromethoxy)benzyl]amino}-2-butanol 21155 (2R,3S)-3-amino-1-[(2-chloro-6-phenoxybenzyl)amino]-4-phenyl-2-butanol 21256 (2R,3S)-3-amino-4-phenyl-1-{[4-(trifluoromethyl)benzyl]amino}-2-butanol 21357 (2R, 3S)-3-amino-1-[(2,3-dichlorobenzyl)amino]-4-phenyl-2-butanol 21458 (2R, 3S)-3-amino-1-[(3,5-dichlorobenzyl)amino]-4-phenyl-2-butanol 21559 (2R, 3S)-3-amino-1-[(3,5-difluorobenzyl)amino]-4-phenyl-2-butanol 21660 (2R,3S)-3-amino-4-phenyl-1-{[4-(trifluoromethoxy)benzyl]amino}-2-butanol 21761 4-({[2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}methyl)benzenesulfonamide 21862 (2R, 3S)-3-amino-1-[(4-methoxybenzyl)amino]-4-phenyl-2-butanol 219 63(2R, 3S)-3-amino-1-[(4-methylbenzyl)amino]-4-phenyl-2-butanol 220 64(2R, 3S)-3-amino-4-phenyl-1-[(3,4,5-trimethoxybenzyl)amino]-2-butanol221 65 (2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethoxy)benzyl]amino}-2-butanol 22266 (2R, 3S)-3-amino-1-[3,5-dimethoxybenzyl)amino]-4-phenyl-2-butanol 22367 (2R, 3S)-3-amino-1-[(2,4-dimethoxybenzyl)amino]-4-phenyl-2-butanol224 68 (2R,3S)-3-amino-1-[([1,1′-biphenyl]-3-ylmethyl)amino]-4-phenyl-2-butanol 22569 (2R, 3S)-3-amino-1-[(3,4-dichlorobenzyl)amino]-4-phenyl-2-butanol 22670 (2R, 3S)-3-amino-1-[(2-fluorobenzyl)amino]-4-phenyl-2-butanol 227 71(2R, 3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanol228 72 (2R, 3S)-3-amino-1-[(2-methylbenzyl)amino]-4-phenyl-2-butanol 22973 (2R, 3S)-3-amino-4-phenyl-1-{[(1R)-1-phenylethyl]amino}-2-butanol 23074 (2R, 3S)-3-amino-4-phenyl-1-{[(1S)-1-phenylethyl]amino}-2-butanol 23175 (2R,3S)-3-amino-1-{[3,5-bis(trifluoromethyl)benzyl]amino}-4-phenyl-2-butanol232 76 (2R,3S)-3-amino-4-phenyl-1-{[2-(trifluoromethyl)benzyl]amino}-2-butanol 23377 (2R,3S)-3-amino-1-{[(1S)-1-(1-naphthyl)ethyl]amino}-4-phenyl-2-butanol 23478 (2R,3S)-3-amino-1-{[(1R)-1-(1-naphthyl)ethyl]amino}-4-phenyl-2-butanol 23579 4-({[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}methyl)-2-methoxyphenol 236 804-({[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}methyl)-1,2-benzenediol 237 81(2R, 3S)-3-amino-1-[(3-methoxypropyl)amino]-4-phenyl-2-butanol 238 82(2R,3S)-3-amino-1-{[(1S)-2-hydroxy-1-methylethyl]amino}-4-phenyl-2-butanol239 83 (2R,3S)-3-amino-1-{[(1R)-2-hydroxy-1-methylethyl]amino}-4-phenyl-2-butanol240 84 (2R, 3S)-3-amino-4-phenyl-1-(2-propynylamino)-2-butanol 241 85(2R, 3S)-3-amino-1-{[2-(2-fluorophenyl)ethyl]amino}-4-phenyl-2-butanol242 86 (2R,3S)-3-amino-1-{[2-(3-fluorophenyl)ethyl]amino}-4-phenyl-2-butanol 243 87(2R, 3S)-3-amino-1-{[2-(4-fluorophenyl)ethyl]amino}-4-phenyl-2-butanol244 88 (2R,3S)-3-amino-1-{[2-(4-bromophenyl)ethyl]amino}-4-phenyl-2-butanol 245 89(2R, 3S)-3-amino-1-{[2-(3-methoxyphenyl)ethyl]amino}-4-phenyl-2-butanol246 90 (2R,3S)-3-amino-1-{[2-(2,4-dichlorophenyl)ethyl]amino}-4-phenyl-2-butanol247 91 (2R,3S)-3-amino-1-{[2-(3-chlorophenyl)ethyl]amino}-4-phenyl-2-butanol 248 92(2R,3S)-3-amino-1-{[2-(2,5-dimethoxyphenyl)ethyl]amino}-4-phenyl-2-butanol249 93 (2R,3S)-3-amino-1-{[2-(4-methylphenyl)ethyl]amino}-4-phenyl-2-butanol 250 94(2R,3S)-3-amino-1-{[(1R)-1-benzyl-2-hydroxyethyl]amino}-4-phenyl-2-butanol251 95 (2R,3S)-3-amino-1-{[3-(4-morpholinyl)propyl]amino}-4-phenyl-2-butanol 252 96(2R, 3S)-3-amino-1-(isobutylamino)-4-phenyl-2-butanol 253 97 (2R,3S)-3-amino-1-{[2-(4-morpholinyl)ethyl]amino}-4-phenyl-2-butanol 254 98(2R, 3S)-3-amino-4-phenyl-1-[(2-hydroxybutyl)amino]-2-butanol 255 99(2R, 3S)-3-amino-4-phenyl-1-{[2-(2-thienyl)ethyl]amino}-2-butanol 256100 4-{[(2R, 3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}-1-butanol 257101 (2R,3S)-3-amino-1-{[(1S)-2-hydroxy-1-phenylethyl]amino}-4-phenyl-2-butanol258 102 (2R,3S)-3-amino-1-[(2,4-dichlorobenzyl)amino]-4-phenyl-2-butanol 259 103(2R,3S)-3-amino-1-{[(1R)-2-hydroxy-1-phenylethyl]amino}-4-phenyl-2-butanol260 104 (2R,3S)-3-amino-1-[(4-tert-butylbenzyl)amino]-4-phenyl-2-butanol 261 105(2R, 3S)-3-amino-4-phenyl-1-[(1-phenylethyl)amino]-2-butanol 262 106(1R, 2S)-1-{[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}-2,3-dihydro-1H-inden-2-ol 263107 (2R, 3S)-3-amino-1-[(3,4-dimethylbenzyl)amino]-4-phenyl-2-butanol264 108 methyl 7-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}heptanoate 265109 2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylpropanamide266 110 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylpropanamide267 111 2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-2-methylpropanamide268 112 2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylacetamide269 113 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylbutanamide270 114 (2R)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylbutanamide271 115 (2R,3S)-3-amino-1-(benzylamino)-4-(3,5-difluorophenyl)-2-butanol 272 116(2R, 3S)-3-amino-4-(3,5-difluorophenyl)-1-(ethylamino)-2-butanol 273 117(2R, 3S)-3-amino-4-(3,5-difluorophenyl)-1-(isobutylamino)-2-butanol 274118 3-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-2-methylpropanamide275 119 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[4-(dimethylamino)benzyl]amino}-2-butanol276 120 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-3-phenylpropanamide277 121 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-3-methylbutanamide278 122 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[2-(dimethylamino)ethyl]amino}-2-butanol279 123 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-pyridinylmethyl)amino]-2-butanol280 124 (2S)-2-{[(2S,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-3-(benzyloxy)-N-isobutylpropanamide281 125 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1-methyl-1-phenylethyl)amino]-2-butanol282 126 (2R)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-3-methylbutanamide283 127 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylpentanamide284 128 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-3-hydroxy-N-isobutylpropanamide285 129 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-phenylethyl)amino]-2-butanol286 130 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-benzylpropanamide287 131 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[(1S)-1-phenylpropyl]amino}-2-butanol 287a 169a  (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-ethylpropanamide288 132 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol289 133 (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-2-phenylethanamide290 134 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-(isopentylamino)-2-butanol 291 135(2R, 3S)-3-amino-1-(cyclohexylamino)-4-(3,5-difluorophenyl)-2-butanol292 136 (2R, 3S)-3-amino-1-(butylamino)-4-(3,5-difluorophenyl)-2-butanol293 137 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxypropyl)amino]-2-butanol294 138 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-hydroxy-2-phenylethyl)amino]-2-butanol295 139 (2R, 3S)-3-amino-4-(3,5-difluorophenyl)-1-{[(3R,5S)-3,5-dimethoxycyclohexyl]amino}-2-butanol 296 140 dimethyl(1R,3S)-5-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylate297 141 (1R, 3S)-5-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylicacid 298 142 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[(1R)-1-phenylpropyl]amino}-2-butanol299 143 (2R,3S)-3-amino-1-[(3-chlorobenzyl)amino]-4-(3,5-difluorophenyl)-2-butanol300 144 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol301 145 (2R,3S)-3-amino-1-[([1,1′-biphenyl]-3-ylmethyl)amino]-4-(3,5-difluorophenyl)-2-butanol302 146 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-iodobenzyl)amino]-2-butanol 303147 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methylbenzyl)amino]-2-butanol304 148 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-phenylpropyl)amino]-2-butanol305 149 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1,3-thiazol-5-ylmethyl)amino]-2-butanol306 150 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-thienylmethyl)amino]-2-butanol307 151 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]-2-butanol308 152 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-pyrazinylmethyl)amino]-2-butanol309 153 (2R,3S)-3-amino-1-[(3,5-difluorobenzyl)amino]-4-(3,5-difluorophenyl)-2-butanol310 154 (2R,3S)-3-amino-1-[(1,3-benzodioxol-5-ylmethyl)amino]-4-(3,5-difluorophenyl)-2-butanol311 155 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3,5-dimethoxybenzyl)amino]-2-butanol312 156 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanol313 157 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-furylmethyl)amino]-2-butanol314 158 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(7-methoxy-1,2,3,4-tetrahydr-1-naphthalenyl)amino]-2-butanol315 159 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethoxy)benzyl]amino}-2-butanol316 160 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-fluorobenzyl)amino]-2-butanol317 161 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-isopropoxybenzyl)amino]-2-butanol318 162 (2R,3S)-3-amino-1-[(3-bromobenzyl)amino]-4-(3,5-difluorophenyl)-2-butanol319 163 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(5-methyl-2-furylmethyl)amino]-2-butanol320 164 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]-2-butanol

Examples 321-473

[1618] Following the general procedure of EXAMPLE 6 and makingnon-critical variations but starting with the amine (VIII) of Column Aand reacting it with the amide forming agent (IX) of Column B, thesubstituted amine (X) of Column C is obtained. Column A Amine (VIII)Column B Column D Compound Amide Forming Column C Physical EXA of EXAAgent (IX) Substitued amine (X) Data 321 170 “PHTH”N¹-[(1S,2R)-1-benzyl-3-(ethylamino)- MH⁺= 2-hydroxypropyl]-N³,N-³- 440.7dipropylisophthalamide 322 171 “PHTH” N¹-[(1S,2R)-1-benzyl-3- MH + =(benzylamino)-2-hydroxypropyl]- 502.7 N³,N³-dipropylisophthalamide 323172 “PHTH” N¹-[(1S,2R)-1-benzyl-2-hydroxy-3- MH + =(isopropylamino)propyl]-N³,N³- 454.6 dipropylisophthalamide 324 173“PHTH” N¹-[(1S,2R)-1-benzyl-2-hydroxy-3- MH + =(4-toluidino)propyl]-N³,N³- 502.2 dipropylisophthalamide 325 174 “P11TH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[2-(4-methoxyphenyl)ethyl]amino} 546propyl)-N³,N³-ipropylisophthalamide 326 175 “PHTH”N^(-{(1S,2R)-1-benzyl-2-hydroxy-3-) MH + =[(3-methoxybenzyl)amino]propyl}- 532 N³,N³-dipropylisophthalamide 327176 “PHTH” ethyl {[(3S)-3-({3-[(dipropylamino) MH + = carbonyl]benzoyl}amino)-2-hydroxy- 574 4-phenylbutyl]amino}(phenyl)acetate 329178 “PHTH” N¹-((1S)-1-benzyl-2-hydroxy-3- MH + ={[(1S)-2-hydroxy-1-(hydroxymethyl)- 6072-(4-nitrophenyl)ethyl]amino}propyl) -N³,N³-dipropylisophthalamide 330179 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(2- MH + = chlorobenzyl)amino]-2- 537hydroxypropyl}-N³,N³- dipropylisophthalamide 331 180 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(4- MH + = chlorobenzyl)amino]-2- 537hydroxypropyl}-N³,N³- dipropylisophthalamide 332 181 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[2-(2-hydroxyethoxy) ethyl]500 amino}propyl)-N³,N³- dipropylisophthalamide 333 182 “PHTH”N¹-[(1S,2R)-1-benzyl-3-(2,3-dihydro- MH + = 1H-inden-1-ylamino)-2- 528hydroxypropyl]-N³,N³- dipropylisophthalamide 334 183 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(2-hydroxypropyl)amino]propyl}- 470 N³,N³-dipropylisophthalamide 335184 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(tetrahydro-2- 496furanylmethyl)amino]propyl}-N³,N³- dipropylisophthalamide 336 185 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(2,2- MH + = diethoxyethyl)amino]-2- 528hydroxypropyl} N³,N³- dipropylisophthalamide 337 186 “PHTH”N¹-[(1S,2R)-1-benzyl-3-(butylamino)- MH + = 2-hydroxypropyl]-N³,N³- 468dipropylisophthalamide 338 187 “PHTH” N¹-[(1S,2R)-1-benzyl-3- MH + =(cyclohexylamino)-2-hydroxypropyl]- 494 N³,N³-dipropylisophthalamide 339188 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(2-pyridinylmethyl)amino]propyl }- 507 N³,N³-dipropylisophthalamide 340189 “PHTH” N¹-{(1S,2R)-3-[(2- MH + = aminobenzyl)amino]-1-benzyl-2- 517hydroxypropyl}-N³,N³- dipropylisophthalamide 341 190 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(3-pyridinylmethyl)amino]propyl}- 503 N³,N³-dipropylisophthalamide 342191 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[2-(1-pyrrolidinyl)ethyl] amino} 509 propyl)-N³,N³-dipropylisophthalamide 343 192 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-MH + = [(2-hydroxy-2- 532 phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide 344 193 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(3- MH + =butoxypropyl)amino]-2- 526 hydroxypropyl}-N³,N³- dipropylisophthalamide345 194 “PHTH” N¹-{(1S,2R)-1-beuzyl-2-hydroxy-3- MH + =[(3-isopropoxypropyl)amino]propyl}- 512 N³,N³-dipropylisophthalamide 346195 “PHTH” N¹-[(1S,2R)-1-benzyl-2-hydroxy-3- MH + =(isopentylamino)propyl]-N³,N³- 482 dipropylisophthalamide 347 196 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(3-phenylpropyl)amino]propyl}-530 N³,N³-dipropylisophthalamide 348 197 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(2-methoxyethyl)amino]propyl}-470 N³,N³-dipropylisophthalamide 349 198 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(2-phenoxyethyl)amino]propyl}-532 N³,N³-dipropylisophthalamide 350 199 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(2-propoxyethyl)amino]propyl}-498 N³,N³-dipropylisophthalamide 351 200 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(3,3- MH + = dimethylbutyl)amino]-2- 496hydroxypropyl}-N³,N³- dipropylisophthalamide 352 201 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(4-phenylbutyl)amino]propyl}-544 N³,N³-dipropylisophthalamide 353 202 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(3-iodobenzyl)amino]propyl}-N³,N³- 628 dipropylisophthalamide 354 203“PHTH” N¹-{(1S)-1-benzyl-2-hydroxy-3-[(4- MH + =nitrobenzyl)amino]propyl}-N³,N³- 547 dipropylisophthalamide 355 204“PHTH” N¹-{(1S,2R)-1-benzyl-3-[(3- MH + = chlorobenzyl)amino]-2- 537hydroxypropyl}-N³,N³- dipropylisophthalamide 356 205 “PHTH”N¹-((1S,2R)-1-benzyl-3-{[2-(4- MH + = chlorophenyl)ethyl]amino}-2- 551hydroxypropyl)-N³,N³- dipropylisophthalamide 357 206 “PHTH”N¹((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[2-(2-pyridinyl)ethyl]amino}propyl)- 517 N³,N³-dipropylisophthalamide358 207 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(4-pyridinylmethyl)amino]propyl}- 503 N³,N³-dipropylisophthalamide 359208 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[2-(1-methyl-2- 523pyrrolidinyl)ethyl]amino}propyl)- N³,N³-dipropylisophthalamide 360 209“PHTH” N¹-{(1S,2R)-1-benzyl-3-[(2,3- MH + = dimethylbenzyl)amino]-2- 580hydroxypropyl}-N³,N³- dipropylisophthalamide 361 210 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[2-(trifluoromethoxy) benzyl]586 amino}propyl)-N³,N³- dipropylisophthalamide 362 211 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(2-chloro-6- MH + = phenoxybenzyl)amino]-2- 629hydroxypropyl}-N³,N³- dipropylisophthalamide 363 212 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[4- 570(trifluoromethyl)benzyl]amino}propyl )-N³,N³-dipropylisophthalamide 364213 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(2,3- MH + = dichlorobenzyl)amino]-2-571 hydroxypropyl}-N³,N³- dipropylisophthalamide 365 214 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(3,5- MH + = dichlorobenzyl)amino]-2- 571hydroxypropyl}-N³,N³- dipropylisophthalamide 366 215 “PHTH”N¹⁻{(1S,2R)-1-benzyl-3-[(3,5- MH + = difluorobenzyl)amino]-2- 538hydroxypropyl}-N³,N³- dipropylisophthalamide 367 216 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[4- 586(trifluoromethoxy)benzyl]amino}prop- yl)-N³,N³-dipropylisophthalamide368 217 “PHTH” N¹-[(1S,2R)-3-({2-[4- MH + =(aminosulfonyl)phenyl]ethyl}amino)- 595 1-benzyl-2-hydroxypropyl]-N³,N³-dipropylisophthalamide 369 218 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-MH + = [(4-methoxybenzyl)amino]propyl}- 532 N³,N³-dipropylisophthalamide370 219 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(4-methylbenzyl)amino]propyl}- 516 N³,N³-dipropylisophthalamide 371 220“PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + = [(3,4,5- 592trimethoxybenzyl)amino]propyl}- N³,N³-dipropylisophthalamide 372 221“PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[3-(trifluoromethoxy)benzyl]amino} 586 propyl)-N³,N³-dipropylisophthalamide 373 222 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(3,5- MH += dimethoxybenzyl)amino]-2- 562 hydroxypropyl}-N³,N³-dipropylisophthalamide 374 223 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(2,4- MH += dimethoxybenzyl)amino]-2- 562 hydroxypropyl}-N³,N³-dipropylisophthalamide 375 224 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[([1,1′-MH + = biphenyl]-3-ylmethyl)amino]-2- 578 hydroxypropyl}-N³,N³-dipropylisophthalamide 376 225 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(3,4- MH += dichlorobenzyl)amino]-2- 571 hydroxypropyl}-N³,N³-dipropylisophthalamide 377 226 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(2- MH + =fluorobenzyl)amino]-2- 520 hydroxypropyl}-N³,N³- dipropylisophthalamide378 227 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[3-(trifluoromethyl)benzyl]amino} 570 propyl)-N³,N³-dipropylisophthalamide 379 228 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-MH + = [(2-methylbenzyl)amino]propyl}- 516 N³,N³-dipropylisophthalamide380 229 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[(1R)-1-phenylethyl]amino}propyl)- 516 N³,N³-dipropylisophthalamide 381230 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[(1S)-1-phenylethyl]amino}propyl)- 516 N³,N³-dipropylisophthalamide 382231 “PHTH” N¹-((1S,2R)-1-benzyl-3-{[3,5- MH + =bis(trifluoromethyl)benzyl]amino}-2- 638 hydroxypropyl)-N³,N³-dipropylisophthalamide 383 232 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3-MH + = {[2-(trifluoromethyl)benzyl]amino} 570 propyl)-N³,N³-dipropylisophthalamide 384 233 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3-MH + = {[(1S)-1-(1- 566 naphthyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide 385 234 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3-MH + = {[(1R)-1-(1- 566 naphthyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide 386 235 “PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-MH + = [(4-hydroxy-3- 548 methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide 387 236 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(3,4- MH + = dihydroxybenzyl)amino]-2- 534hydroxypropyl}-N³,N³- dipropylisophthalamide 388 237 “PHTH”N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3- MH + =methoxypropyl)amino]propyl}-N³,N³- 484 dipropylisophthalamide 389 238“PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[(1S)-2-hydroxy-1- 470methylethyl]amino}propyl)-N³,N³- dipropylisophthalamide 390 239 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[(1R)-2-hydroxy-1- 470methylethyl]amino}propyl)-N³,N³- dipropylisophthalamide 391 240 “PHTH”N¹-[(1S,2R)-1-benzyl-2-hydroxy-3- MH + = (2-propynylamino)propyl]-N³,N³-450 dipropylisophthalamide 392 241 “PHTH” N¹-((1S,2R)-1-benzyl-3-{[2-(2-MH + = fluorophenyl)ethyl]amino}-2- 534 hydroxypropyl)-N³,N³-dipropylisophthalamide 393 242 “PHTH” N¹-((1S,2R)-1-benzyl-3-{[2-(3-MH + = fluorophenyl)ethyl]amino}-2- 534 hydroxypropyl)-N³,N³-dipropylisophthalamide 394 243 “PHTH” N¹-((1S,2R)-1-benzyl-3-{[2-(4-MH + = fluorophenyl)ethyl]amino}-2- 534 hydroxypropyl)-N³,N³-dipropylisophthalamide 395 244 “PHTH” N¹-((1S,2R)-1-benzyl-3-{[2-(4-MH + = bromophenyl)ethyl]amino}-2- 595 hydroxypropyl)-N³,N³-dipropylisophthalamide 396 245 “PHTH” N¹-((1S)-1-benzyl-2-hydroxy-3-{[2-MH + = (3- 546 methoxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide 397 246 “PHTH”N¹-((1S,2R)-1-benzyl-3-{[2-(2,4- MH + = dichlorophenyl)ethyl]amino}-2-585 hydroxypropyl)-N³,N³- dipropylisophthalamide 398 247 “PHTH”N¹-((1S,2R)-1-benzyl-3-{[2-(3- MH + = chlorophenyl)ethyl]amino}-2- 551hydroxypropyl)-N³,N³- dipropylisophthalamide 399 248 “PHTH”N¹-((1S)-1-benzyl-3-{[2-(2,5- MH + = dimethoxyphenyl)ethyl]amino}-2- 576hydroxypropyl)-N³,N³- dipropylisophthalamide 400 249 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[2-(4- 530methylphenyl)ethyl]amino}propyl)- N³,N³-dipropylisophthalamide 401 250“PHTH” N¹-((1S,2R)-1-benzyl-3-{[(1R)-1- MH + =benzyl-2-hydroxyethyl]amino}-2- 546 hydroxypropyl)-N³,N³-dipropylisophthalamide 402 251 “PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3-MH + = {[3-(4- 539 morpholinyl)propyl]amino}propyl)-N³,N³-dipropylisophthalamide 403 252 “PHTH”N¹-[(1S,2R)-1-benzyl-2-hydroxy-3- MH + = (isobutylamino)propyl]-N³,N³-468 dipropylisophthalamide 404 253 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[2-(4- 525morpholinyl)ethyl]amino}propyl)- N³,N³dipropylisophthalamide 405 254“PHTH” N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(2-hydroxybutyl)amino]propyl}- 484 N³,N³dipropylisophthalamide 406 255“PHTH” N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + ={[2-(2-thienyl)ethyl]amino}propyl)- 522 N³,N³-dipropylisophthalamide 407256 “PHTH” N¹{(1S,2R)-1-benzyl-2-hydroxy-3- MH + =[(4-hydroxybutyl)amino]propyl}- 484 N³,N³-dipropylisophthalamide 408 257“PHTH” N¹((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[(1S)-2-hydroxy-1- 532phenylethyl]amino}propyl)-N³,N³- dipropylisophthalamide 409 258 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(2,4- MH + = dichlorobenzyl)amino]-2- 571hydroxypropyl}-N³,N³- dipropylisophthalamide 410 259 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH + = {[(1R)-2-hydroxy-1- 532phenylethyl]amino}propyl)-N³,N³- dipropylisophthalamide 411 260 “PHTH”N¹-{(1S,2R)-1-benzyl-3-[(4-tert- MH⁺ = butylbenzyl)amino]-2- 558hydroxypropyl}-N³,N³- dipropylisophthalamide 412 261 “PHTH”N¹-{(1S,2R)-1-benzyl-2-hydroxy-3- MH⁺ = [(1-phenylethyl)amino]propyl}-516 N³,N³-dipropylisophthalamide 413 262 “PHTH”N¹-((1S,2R)-1-benzyl-2-hydroxy-3- MH⁺ ={[(1R,2S)-2-hydroxy-2,3-dihydro-1H- 544 inden-1-yl]amino}propyl)-N³,N³-dipropylisophthalamide 414 263 “PHTH” N¹-{(1S,2R)-1-benzyl-3-[(3,4- MH⁺= dimethylbenzyl)amino]-2- 530 hydroxypropyl}-N³,N³-dipropylisophthalamide 416 265 “PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[2-(isobutylamino)-1- 575 methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide 417 266 “PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(1S)-2-(isobutylamino)- 5751-methyl-2-oxoethyl]amino}propyl)- N³,N³-dipropylisophthalamide 418 266“3,5-pyridinyl” N³-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(1S)-2-(isobutylamino)- 5761-methyl-2-oxoethyl]amino}propyl)- N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide 419 267 “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[2-(isobutylamino)-1,1- 603dimethyl-2-oxoethyl]amino}propyl)- 5-methyl-N³,N³-dipropylisophthalamide 420 268 “5-Me-PH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[2-(isobutylamino)-2- 575.3 oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 421 269 “5-Me-PHTH”N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + = hydroxy-3-({(1S)-1- 603.8[(isobutylamino)carbonyl]propyl}ami- no)propyl]-5-methyl-N³,N³-dipropylisophthalamide 422 270 “5-Me-PHTH”N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + = hydroxy-3-({(1R)-1- 603.8[(isobutylamino)carbonyl]propyl}ami- no)propyl]-5-methyl-N³,N³-dipropylisophthalamide 423 271 “5-Me-PHTH”N¹-[(1S,2R)-3-(benzylamino)-1-(3,5- MH + =difluorobenzyl)-2-hydroxypropyl]-5- 552.3methyl-N³,N³-dipropylisophthalamide 424 272 “5-Me-PHTH”N¹[(1S,2R)-1-(3,5-difluorobenzyl)-3- MH + =(ethylamino)-2-hydroxypropyl]-5- 490.7methyl-N³,N³-dipropylisophthalamide 425 273 “5-Me-PHTH”N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-(isobutylamino)propyl]-5- 518.0methyl-N³,N³-dipropylisophthalamide 426 274 “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[3-(isobutylamino)-2- 603 methyl-3-oxopropyl]amino}propyl)-5-methyl-N³,N³- dipropylisophthalamide 427 275 “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3- MH + ={[4-(dimethylamino)benzyl]amino}- 595.8 2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide 428 276 “5-Me-PHTH”N¹-[(1S,2R)-3-{[(1S)-1-benzyl-2- MH + =(isobutylamino)-2-oxoethyl]amino}- 665.9 1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³- dipropylisophthalamide 429 277“5-Me-PHTH” N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-({(1S)-1- 617.9 [(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5- methyl-N³,N³-dipropylisophthalamide 430278 “5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3- MH + ={[2-(dimethylamino)ethyl]amino}-2- 533.3 hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide 431 279 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 2-hydroxy-3-[(3- 553pyridinylmethyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide 432280 “5-Me-PHTH” N¹-[(1S,2R)-3-{[(1S)-1- MH + = [(benzyloxy)methyl]-2-695.9 (isobutylamino)-2-oxoethyl]amino}- 1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³- dipropylisophthalamide 433 281“5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(1-methyl-1- 580.8 phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 434 282 “5-Me-PHTH”N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + = hydroxy-3-({(1R)-1- 617.9[(isobutylamino)carbonyl]-2- methylpropyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide 435 283 “5-Me-PHTH”N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + = hydroxy-3-({(1S)-1- 617.9[(isobutylamino)carbonyl]butyl}amino) propyl]-5-methyl-N³,N³-dipropylisophthalamide 436 284 “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(1S)-1-(hydroxymethyl)- 605.8 2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl N³,N³-dipropylisophthalamide 437 285“5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 2-hydroxy-3-[(2-566.8 phenylethyl)amino]propyl}-5-methyl- N³,N³-dipropylisophthalamide438 286 “5-Me-PHTH” N¹-[(1S,2R)-3-{[(1S)-2- MH + =(benzylamino)-1-methyl-2- 623.2 oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5- methyl-N³,N³-dipropylisophthalamide439 287 “5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(1S)-1- 580.8 phenylpropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 440 287a “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3- MH + ={[(1S)-2-(ethylamino)-1-methyl-2- 561.2oxoethyl]amino}-2-hydroxypropyl)- 5-methyl-N³,N³- dipropylisophthalamide441 289 “5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(1S)-2-(isobutylamino)- 651.92-oxo-1-phenylethyl]amino}propyl)- 5-methyl-N³,N³-dipropylisophthalamide 442 290 “5-Me-PHTH”N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-(isopentylamino)propyl]- 531.69 5-methyl-N³,N³-dipropylisophthalamide 443 291 “5-Me-PHTH”N¹-[(1S,2R)-3-(cyclohexylamino)-1- MH + = (3,5-difluorobenzyl)-2- 544.2hydroxypropyl]-5-methyl-N³,N³- dipropylisophthalamide 444 292“5-Me-PHTH” N¹-[(1S,2R)-3-(butylamino)-1-(3,5- MH + =difluorobenzyl)-2-hydroxypropyl]-5- 518.2methyl-N³,N³-dipropylisophthalamide 445 293 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 2-hydroxy-3-[(3- 534.2methoxypropyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide 446294 “5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(2-hydroxy-2- 582 phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 447 295 “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3- MH + = {[(3R,5S)-3,5- 604.2dimethoxycyclohexyl]amino}-2- hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide 448 296 “5-Me-PHTH” dimethyl(1R,3S)-5-{[(2R,3S)-4-(3,5- MH + = difluorophenyl)-3-({3- 660.2[(dipropylamino)carbonyl]-5- methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3- cyclohexanedicarboxylate 449 297 “5-Me-PHTH”(1R,3S)-5-{[(2R,3S)-4-(3,5 MH + = difluorophenyl)-3-({3- 632.2[(dipropylamino)carbonyl]-5- methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3- cyclohexanedicarboxylic acid 450 298“5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(1R)-1- 580.8 phenylpropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 451 299 “5-Me-PHTH”N¹-[(1S,2R)-3-[(3- MH + = chlorobenzyl)amino]-1-(3,5- 586.3difluorobenzyl)-2-hydroxypropyl]-5- methyl-N³,N³-dipropylisophthalamide452 300 “-SO₂-” N-{(1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-[(3- 603.2 methoxybenzyl)amino]propyl}-3-[(2-propylpentyl)sulfonyl]benzamide 453 301 “5-Me-PHTH”N¹{(1S,2R)-3-[([1,1′-biphenyl]-3- MH + = ylmethyl)amino]-1-(3,5- 628.8difluorobenzyl)-2-hydroxypropyl]-5- methyl-N³,N³-dipropylisophthalamide454 302 “5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(3- 678 iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 455 303 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 2-hydroxy-3-[(3- 566.8methylbenzyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide 456304 “5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(2- 694 phenylpropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 457 305 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 2-hydroxy-3-[(1,3-thiazol-5-559.5 ylmethyl)amino]propyl}-5-methyl- N³,N³-dipropylisophthalamide 458306 “5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(2- 558.5 thienylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 459 307 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(5-methoxy-1,2,3,4- 814 tetrahydro-1-naphthalenyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide 460308 “5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(2- 554.3 pyrazinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 461 309 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =3-[(3,5-difluorobenzyl)amino]-2- 588.7 hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide 462 310 “PHTH” N¹-{(1S,2R)-3-[(1,3-benzodioxol-5-MH + = ylmethyl)amino]-1-benzyl-2- 546 hydroxypropyl}-N³,N³-dipropylisophthalamide 463 311 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =3-[(3,5-dimethoxybenzyl)amino]-2- 612.4 hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide 464 312 “5-Me-PHTH”N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + = hydroxy-3-{[3- 620.3(trifluoromethyl)benzyl]amino}propyl )-5-methyl-N³,N³-dipropylisophthalamide 466 314 “5-Me-PHTH” Racemic N¹-{(1S,2R)-1-(3,5-MH+ = difluorobenzyl)-2-hydroxy-3-[(7 814 methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide 467315 “5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[3- 636.3 (trifluoromethoxy)benzyl]amino}prop-yl)-5-methyl-N³,N³- dipropylisophthalamide 468 316 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 3-[(3-fluorobenzyl)amino]-2-570.3 hydroxypropyl}-5-methyl-N³,N³- dipropylisophthalamide 469 317“5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + = 2-hydroxy-3-[(3-610.4 isopropoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 470 318 “5-Me-PHTH”N¹-[(1S,2R)-3-[(3- MH + = bromobenzyl)amino]-1-(3,5- 631.6difluorobenzyl)-2-hydroxypropyl]-5- methyl-N³,N³-dipropylisophthalamide471 319 “5-Me-PHTH” N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2- MH + =hydroxy-3-{[(5-methyl-2- 556 furyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 472 320 “5-Me-PHTH”N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH + =2-hydroxy-3-[(5-methoxy-1,2,3,4- 622 tetrahydro-1-naphthalenyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide“isomer A” 473 320 “5-Me-PHTH” N¹-{(1S,2R)-1-(3,5-difluorobenzyl)- MH⁺ =2-hydroxy-3-[(5-methoxy-1,2,3,4- 622 tetrahydro-1-naphthalenyl)amino]propyl}-5- methyl-N³,N³-dipropylisophthalamide“isomer B”

Example 474N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(1,2,3,4-tetrahydro-1-naphthalenylamino)propyl]-N³,N³-dipropylisophthalamide(X)

[1619] Following the general procedures of EXAMPLEs 6 and 321473 andmaking non-critical variations but starting with(2R,3S)-3-amino-4-phenyl-1-(1,2,3,4-tetrahydro-1-naphthalenylamino-2-butanol(VIII) and using “PHTH”, the title compound is obtained, MH⁺=542.3.

Examples 475-483

[1620] Following the general procedure of EXAMPLE 6 and makingnon-critical variations but starting with the amine (VIII) of Column Aand reacting it with the amide forming agent (IX) of Column B, thesubstitute amine (X) of Column C is obtained. Column A Amine (VIII)Column B Column D Compound Amide Forming Column C Physical EXA of EXAAgent (IX) Substitued amine (X) Data 475 271 “5-OMe-PHTH”N¹-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl]-5- 568.2 methoxy-N³,N³-dipropylisophthalamide 476 271 “PHTH”N¹-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl]- 538.2 N³,N³-dipropylisophthalamide 477271 “5-Cl-PHTH” N¹-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl]-5- 572.1chloro-N³,N³-dipropylisophthalamide 478 271 “3,5-pyridinyl”N³-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl]- 539.5 N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide 479 271 “5-F-PHTH”N¹-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl]-5- 556.3fluoro-N³,N³-dipropylisophthalamide 480 271 “thienyl”N²-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl]- 544.2 N⁵,N⁵-dipropyl-2,5-thiophenedicarboxamide 481 271 “2,4-pyridinyl”N⁴-[(1S,2R)-3-(benzylamino)-1-(3,5- MH⁺ =difluorobenzyl)-2-hydroxypropyl- 539.3 N²,N²-dipropyl-2,4-pyridinedicarboxamide 482 271 “4,6- N⁴-[(1S,2R)-3-(benzylamino)-1-(3,5-MH + = pyrimidinyl” difluorobenzyl)-2-hydroxypropyl]- 540N⁶,N⁶dipropyl-4,6- pyrimidinedicarboxamide 483 271 “morpholinyl”N-[(1S,2R)-3-(benzylamino)-1-(3,5- MH + =difluorobenzyl)-2-hydroxypropyl]-3- 552 (4-morpholinylcarbonyl)benzamide

Example 484N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide(X)

[1621] Following the general procedures of EXAMPLEs 4 and 14-107 andmaking non-critical variations but starting with tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V, commercially available) andNH₂—CH₂-phenyl-(3—CH₃) (VI), the corresponding protected alcohol (VII)is obtained.

[1622] Following the general procedure of EXAMPLEs 5 and 170-320 andmaking non-critical variations, the corresponding amine (VIII) isobtained.

[1623] Following the general procedure of EXAMPLEs 6 and 321-483 andmaking non-critical variations but using “PHTH” (IX), the title compoundis obtained, MH⁺=516.

Example 485N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide(X)

[1624] Following the general procedure of EXAMPLEs 6 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol(VIII, EXAMPLE 5) with 5-(dipropylamino)-5-oxopentanoic acid (DX), thetitle compound is obtained, MH⁺=534.2.

Example 486N¹-[(1S,2R)-3-{[(1R)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1625] Following the general procedures of EXAMPLEs 124, 280 and 432 andmaking non-critical variations but using the “R” C-terminal amine (VI),the title compound is obtained, MH⁺=695.

Example 487N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide(X)

[1626] Following the general procedures of EXAMPLEs 128, 284 and 436 andmaking non-critical variations but using the “R″ C-terminal amine (VI),the title compound is obtained, MH⁺=719.

Example 488N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(pentylamino)propyl]-N³,N³-dipropylisophthalamide(X)

[1627] Following the general procedures of EXAMPLEs 96, 252 and 403 andmaking non-critical variations but using NH₂—(CH₂)₄—CH₃ as theC-terminal amine (VI), the title compound is obtained, MH⁺=481.

Example 489N¹-[(1S)-3-({2-[4-(aminosulfonyl)phenyl]ethyl}amino)-1-benzyl-2-hydroxypropyl]-N³,N³-dipropylisophthalamide(X)

[1628] Following the general procedures of EXAMPLEs 61, 217 and 368 andmaking non-critical variations but using racemic C-terminal amine (VI),the title compound is obtained, MH⁺=595.

Example 491N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide(X)

[1629] Following the general procedure of EXAMPLE 457 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1,3-thiazol-5-ylmethyl)amino]-2-butanol(VIII, EXAMPLE 305) with “3,5-pyridinyl” as the amide forming agent(IX), the title compound is obtained.

Example 4923-Benzoyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide(X)

[1630] Following the general procedure of EXAMPLE 452 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoltrifluoroacetate (VIII, EXAMPLE 5) and reacting it withphenyl-CO-phenyl-CO—OH (IX) where the attachment to the -phenyl-ring is1,3- for the carbonyl groups, the title compound is obtained, MH⁺=545.2.

Example 493N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}[1,1′-biphenyl]-3-carboxamide(X)

[1631] Following the general procedure of EXAMPLE 452 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoltrifluoroacetate (VIII, EXAMPLE 5) and reacting it withphenyl-phenyl-CO—OH (IX) where the attachment to the middle- phenyl-ringis 1,3- for the carbonyl group and other- phenyl , the title compound isobtained, MH⁺=517.2.

Example 494N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino}propyl]-N³,N³-dipropylisophthalamide(X)

[1632] Following the general procedure of EXAMPLE 452 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoltrifluoroacetate (VIII, EXAMPLE 5) and reacting it with(CH₃—O—CH₂—CH₂—)₂N—CO—CO—OH (IX) where the attachment to the-phenyl-ring is 1,3- for the carbonyl groups, the title compound isobtained, MH⁺=570.3.

Example 495N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-(2-methoxyethyl)-N3-propylisophthalamide(X)

[1633] Following the general procedure of EXAMPLE 452 and makingnon-critical variations and using(2R,3S)-3-amino-1-(benzylamino)-4-(3,5-difluorophenyl)-2-butanol (VIII,EXAMPLE 271) and reacting it with(CH₃—CH₂—CH₂—)(CH₃—O—CH₂—CH₂—)N—CO-phenyl-CO—OH (IX) where theattachment to the -phenyl-ring is 1,3- for the carbonyl groups, thetitle compound is obtained, MH⁺=554.5.

Example 496N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-ethoxybenzamide(X)

[1634] Following the general procedure of EXAMPLE 452 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoltrifluoroacetate (VIII, EXAMPLE 5) and reacting it withCH₃—CH₂—O-phenyl-CO—OH (IX) where the attachment to the -phenyl-ring is1,3- for the carbonyl and ethoxy group, the title compound is obtained,MH⁺=485.

Example 497N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-naphthamide(X)

[1635] Following the general procedure of EXAMPLE 452 and makingnon-critical variations and using(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoltrifluoroacetate (VIII, EXAMPLE 5) and reactinortho position, the titlecompound is obtained, MH⁺=491.

Example 498N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1R)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1636] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 1,2,3,4-tetrahydro-1-naphthalenylamine (VI) and “5-Me-PHTH” (IX),the title compound is obtained, MH⁺=588.

Example 499N¹-[(1R)-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1637] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), H₂N—CH₂-phenyl-(3,5-ditrifluoromethyl) (VI) and “5-Me-PHTH” (IX),the title compound is obtained, MH⁺=688.

Example 500N¹-((1S,2R)-1-benzyl-3-{[2-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1638] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(2-fluoro-5-trifluoromethyl) (VI) and “PHTH” (IX), thetitle compound is obtained, MH⁺=588.

Example 501N¹-{(1S,2R)-1-benzyl-3-[(2,3-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide(X)

[1639] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), H₂N—CH₂-phenyl-(2,3-difluoro)(VI) and “PHTH” (IX), the title compound is obtained, MH⁺=538.

Example 502N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-4-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1640] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(3-fluoro-4-trifluoromethyl) (VI) and “PHTH” (IX), thetitle compound is obtained, MH⁺=588.

Example 503N¹-{(1S,2R)-1-benzyl-3-[(2,5-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide(X)

[1641] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), H₂N—CH₂-phenyl-(2,5-difluoro)(VI) and “PHTH” (IX), the title compound is obtained, MH⁺=538.

Example 504N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1642] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(3-fluoro-5-trifluoromethyl) (VI) and “PHTH” (IX), thetitle compound is obtained, MH⁺=588.

Example 505N¹-{(1S,2R)-1-benzyl-3-[(3,4-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide(X)

[1643] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), H₂N—CH₂-phenyl-(3,4-difluoro)(VI) and “PHTH” (IX), the title compound is obtained, MH⁺=538.

Example 506N¹-((1S,2R)-1-benzyl-3-{[4-fluoro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1644] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(3-trifluoromethyl4-fluoro) (VI) and “PHTH” (IX), thetitle compound is obtained, MH⁺=588.

Example 507N¹-((1S,2R)-1-benzyl-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1645] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(2-chloro-5-trifluoromethyl) (VI) and “PHTH” (IX), thetitle compound is obtained, MH⁺=605.

Example 508N¹-((1S,2R)-1-benzyl-3-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1646] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(3-trifluoromethyl-4-chloro) (VI) and “PHTH” (IX), thetitle compound is obtained, MH⁺=605.

Example 509N¹-[(1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-2-ylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide(X)

[1647] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N-(2,3-dihydro-1H-inden-2-yl) and “PHTH” (IX), the title compound isobtained, MH⁺=528.

Example 510N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide(X)

[1648] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), H₂N—CH₂-phenyl-3-nitro (VI)and “PHTH” (IX), the title compound is obtained, MH⁺=547.

Example 511N¹-((1S,2R)-1-benzyl-3-{[3-(difluoromethoxy)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide(X)

[1649] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 1H₂N—CH₂-phenyl-3(-O—CHF₂)(VI) and “PHTH” (IX), the title compound is obtained, MH⁺=538.

Example 512N¹-{(1S,2R)-1-benzyl-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide(X)

[1650] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), H₂N—CH₂-phenyl-(3—O—CH₂—CH₃)(VI) and “PHTH” (IX), the title compound is obtained, MH⁺=546.

Example 513N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(5-methyl-2-pyrazinyl)methyl]amino}propyl)-N³,N³-dipropylisophthalamide(X)

[1651] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 5-methyl-2-methylaminoprazine(VI) and “PHTH” (IX), the title compound is obtained, MH⁺=518.

Example 514N¹-{(1S,2R)-1-benzyl-3-[(3-bromo-4-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide(X)

[1652] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V),H₂N—CH₂-phenyl-(3-bromo-4-fluoro) (VI) and “PHTH” (IX), the titlecompound is obtained, MH⁺=599.

Example 515N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1653] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-phenyl-(3,5-dimethyl) (VI) and “5-Me-PHTH” (IX), the titlecompound is obtained, MH⁺=580.

Example 516N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1654] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-phenyl-(3-ethoxy) (VI) and “5-Me-PHTH” (IX), the title compoundis obtained, MH⁺=596.

Example 517N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1655] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂—CH₂—O-phenyl (VI) and “5-Me-PHTH” (IX), the title compound isobtained, MH⁺=582.

Example 518N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isobutoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1656] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-phenyl-O-1-butyl (VI) and “5-Me-PHTH” (IX), the title compoundis obtained, MH⁺=624.

Example 519N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-methyl-1,3-thiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide(X)

[1657] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-4-methyl-1,3-thiazol-2-yl (VI) and “5-Me-PHTH” (IX), the titlecompound is obtained, MH⁺=573.

Example 520N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-methyl-N³-propylisophthalamide(X)

[1658] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-phenyl (VI) and (CH₃—CH₂—CH₂—)(CH₃—)N—CO—(CH₃—)phenyl-CO—OH (IX)where the attachment to the -phenyl-ring for the carbonyls is 1-,3- and5- for the methyl group, the title compound is obtained, MH⁺=510.

Example 521N²-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-2,5-furandicarboxamide(X)

[1659] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-phenyl (VI) and (CH₃—CH₂—CH₂—)₂N—CO—(2,5-furanyl)—CO— (IX), thetitle compound is obtained, MH⁺=528.

Example 522N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide(X)

[1660] Following the general procedure of EXAMPLEs 4,5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—CH₂-phenyl-3-trifluoromethyl (VI) and “3,5-pyridinyl” (IX), thetitle compound is obtained, MH⁺=607.

Example 523N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide(X)

[1661] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),H₂N—C(-CH₃)₂-phenyl (VI) and “3,5-pyridinyl” (IX), the title compound isobtained, MH⁺=567.

Example 524N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1662] Following the general procedure of CHARTs A, C and D and EXAMPLEs165-168 and making non-critical variations, but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V) and“5-Me-PHTH” (IX), the title compound is obtained, MH⁺=462.

Example 525N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1,2-diphenylethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1663] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),NH₂—CH(—CH₂-phenyl (VI) and “5-Me-PHTH” (IX), the title compound isobtained, MH⁺=642.

Example 526N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide,isomer A (X)

[1664] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),7-methoxy-1,2,3,4-tetrahydro-1-naphthalenylamine (VI) and “5-Me-PHTH”(IX), the title compound is obtained, MH⁺=622.

Example 527N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide,isomer B (X)

[1665] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),7-methoxy-1,2,3,4-tetrahydro-1-naphthalenylamine (VI) and “5-Me-PHTH”(IX), the title compound is obtained, MH⁺=622.

Example 528Benzyl-(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate(XII)

[1666] Following the general procedure of EXAMPLE 165 and makingnon-critical variations but starting with benzyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE13), the title compound is obtained.

Example 529N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(dimethylamino)benzamide(X)

[1667] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-dimethylaminobenzoic acid (IX), the title compound is obtained,MH⁺=448.

Example 530N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-2-methyl-1H-benzimidazole-5-carboxamide(X)

[1668] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and2-methyl-1H-benzimidazole-5-carboxylic acid (IX), the title compound isobtained, MH⁺=459.

Example 5313-(aminosulfonyl)-N-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-chlorobenzamide(X)

[1669] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-(aminosulfonyl)-4-chlorobenzoic acid (IX), the title compound isobtained, MH⁺=519.

Example 532N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-cyanobenzamide(X)

[1670] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-cyanobenzoic acid (IX), the title compound is obtained, MH⁺=430.

Example 533N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-4-chloro-3-nitrobenzamide(X)

[1671] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-chloro-3-nitrobenzoic acid (IX), the title compound is obtained,MH⁺=484.

Example 534 Methyl3-[({(S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-nitrobenzoate(X)

[1672] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-nitro-5-(methyl-O—CO—)-phenyl-CO—OH (IX), the title compound isobtained, MH⁺=508.

Example 535 tert-butyl3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-phenylcarbamate(X)

[1673] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-(t-butyl-O—CO—NH)-phenyl-CO—OH (IX), the title compound is obtained,MH⁺=520.

Example 536N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-9,10-dioxo-9,10-dihydro-2-anthourancenylcarboxamide(X)

[1674] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and9,10-dioxo-9,10-dihydro-2-anthourancenylcarboxylic acid (IX), the titlecompound is obtained, MH⁺=535.

Example 537N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-1H-1,2,3-benzotriazole-6-carboxamide(X)

[1675] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and1H-1,2,3-benzotriazolyl-6-carboxylic acid (IX), the title compound isobtained, MH⁺=446.

Example 538N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzamide(X)

[1676] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-(3-methyl-5-oxo4,5-dihydro-1H-pyrazol-1-yl)benzoic acid (IX), thetitle compound is obtained, MH⁺=501.

Example 539N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-1H-indole-5-carboxamide(X)

[1677] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) andindole-5-carboxylic acid (IX), the title compound is obtained, MH⁺=444.

Example 540N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-fluoro-5-(trifluoromethyl)benzamide(X)

[1678] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-fluoro-5-(trifluoromethyl)benzoic acid (IX), the title compound isobtained, MH⁺=491.

Example 541N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-3-(trifluoromethyl)benzamide(X)

[1679] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-(trifluoromethyl)benzoic acid (IX), the title compound is obtained,MH⁺=473.

Example 542N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-4-(butylamino)benzamide(X)

[1680] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-(butylamino)benzoic acid (IX), the title compound is obtained,MR⁺=476.

Example 543N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-3-(trifluoromethoxy)benzamide(X)

[1681] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-(trifluoromethoxy)benzoic acid (IX), the title compound is obtained,MH⁺=489.

Example 544N-{(S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-3,5-dimethoxybenzamide(X)

[1682] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3,5-dimethoxybenzoic acid (IX), the title compound is obtained, MH⁺=465.

Example 545N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-3,5-dimethylbenzamide(X)

[1683] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3,5-dimethylbenzoic acid (IX), the title compound is obtained, MH⁺=433.

Example 546N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-3,5-difluorobenzamide(X)

[1684] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3,5-difluorobenzoic acid (IX), the title compound is obtained, MH⁺=441.

Example 547N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-3,5-dichlorobenzamide(X)

[1685] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3,5-dichlorobenzoic acid (IX), the title compound is obtained, MH⁺=474.

Example 548N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-4-(benzyloxy)benzamide(X)

[1686] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-(benzyloxy)benzoic acid (IX), the title compound is obtained, MH⁺=511.

Example 549N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-1,3-benzodioxole-5-carboxamide(X)

[1687] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and1,3-benzodioxole-5-carboxylic acid (IX), the title compound is obtained,MH⁺=449.

Example 5503-(acetylamino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide(X)

[1688] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-(acetylamino)benzoic acid (IX), the title compound is obtained,MH⁺=462.

Example 5514-(acetylamino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide(X)

[1689] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-(acetylamino)benzoic acid (IX), the title compound is obtained,MH⁺=462.

Example 552N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3,5-dimethyl-4-isoxazolyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide(X)

[1690] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 3,5-dimethyl4-isoxazolylmethylamine (VI) and “5-Me-PHTH” (IX), thetitle compound is obtained, MH⁺=571.3.

Example 553N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-phenylpropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1691] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 3-phenylpropyl)amine (VI) and “5-Me-PHTH” (IX), the title compoundis obtained, MH⁺=580.

Example 554N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1692] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 3-furylmethylamine (VI) and “5-Me-PHTH” (IX), the title compound isobtained, MH⁺=542.

Example 555N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-3-furanylmethyl)amino]propyl}-5-methyl-N3,N³-dipropylisophthalamide(X)

[1693] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (tetrahydro-3-furanylmethyl)amine (VI) and “5-Me-PHTH” (IX), thetitle compound is obtained, MH+546.

Example 556N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-propoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1694] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (3-propoxybenzyl)amine (VI) and “5-Me-PHTH” (IX), the title compoundis obtained, MH⁺=610.

Example 557N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1695] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (2-pyridinylmethyl)amine (VI) and “5-Me-PHTH” (IX), the titlecompound is obtained, MH⁺=553.

Example 558N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-hydroxy-N³,N³-dipropylisophthalamide(X)

[1696] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), benzylamine (VI) and 5-hydroxy-N,N-dipropylisophthalic acid (IX),the title compound is obtained, MH⁺=554.

Example 559N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-methyl-1-(3-methylphenyl)ethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide(X)

[1697] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), [1-methyl-1-(3-methylphenyl)ethyl]amine (VI) and “5-Me-PHTH” (IX),the title compound is obtained, MH⁺=594.

Example 560N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1S)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1698] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (1S)-1,2,3,4-tetrahydro-1-naphthalenylamine (VI) and “5-Me-PHTH”(IX), the title compound is obtained, MH⁺=592.

Example 561N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1699] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 2,5-dimethylbenzylamine (VI) and “5-Me-PHTI” (IX), the titlecompound is obtained, MH⁺=580.

Example 562N¹-[(1S,2R)-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1700] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 2-chloro-5-trifluorobenzylamine (VI) and “5-Me-PHTH” (IX), the titlecompound is obtained, MH⁺=654.

Example 563N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-5-methylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1701] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), 2-hydroxy-5-methylbenzylamine (VI) and “5-Me-PHTH” (IX), the titlecompound is obtained, MH⁺=582.

Example 564N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide(X)

[1702] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amine (VI) and“5-Me-PHTH” (DX), the title compound is obtained, MH⁺=594.

Example 565N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1703] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (1R)-2,3-dihydro-1H-inden-1-ylamine (VI) and “5-Me-PHTH” (IX), thetitle compound is obtained, MH⁺=578.

Example 5665-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide(X)

[1704] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (1-methyl-1-phenylethyl)amine (VI) and “5-Cl-PHTH” (IX), the titlecompound is obtained, MH⁺=601.

Example 567N¹-[(1S,2R)-3-[(1-benzofuran-2-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1705] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (1-benzofuran-2-ylmethyl)amine (VI) and “5-Me-PHTH” (IX), the titlecompound is obtained, MH⁺=592.

Example 568N¹-[(1S,2R)-3-{[(1R)-1-(3-bromophenyl)ethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1706] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3), (1R)-1-(3-bromophenyl)ethyl]amine (VI) and “5-Me-PHTH” (IX), thetitle compound is obtained, MH⁺=645.

Example 569N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1707] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(4-fluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),3-iodobenzylamine (VI) and “5-Me-PHTH” (IX), the title compound isobtained, MH⁺=660.

Example 570N-{(S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyl(butyryl)amino]-5-methylbenzamide(X)

[1708] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and3-[butyl(butyryl)amino]-5-methylbenzoic acid (IX), the title compound isobtained, MH⁺=560.

Example 571N¹-{1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide(X)

[1709] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-methyl-N,N-dipropylisophthalic acid (IX), the title compound isobtained, MH⁺=546.

Example 572N³-{1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N¹,N¹-dipropylisophthalamide(X)

[1710] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and4-methyl-N,N-dipropylisophthalic acid (IX), the title compound isobtained, MH⁺=546.

Example 573N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide(X)

[1711] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),3-methoxybenzylamine (VI) and 4-methyl-N,N-dipropylisophthalic acid(IX), the title compound is obtained, MH⁺=582.

Example 574N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-butyl-1H-indole-6-carboxamide(X)

[1712] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl1-(2-oxiranyl)-2-phenylethylcarbamate (V), 3-methoxybenzylamine (VI) and1-butyl-1H-indole-6-carboxylic acid (IX), the title compound isobtained, MH⁺=500.

Example 575N¹-[(S,2R)-3-anilino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide(X)

[1713] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V), aniline(VI) and and “5-Me-PHTH” (IX), the title compound is obtained, MH⁺=538.

Example 5765-bromo-N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide(X)

[1714] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),3-bromobenzylamine (VI) and 5-bromo-N,N-dipropylisophthalic acid (IX),the title compound is obtained, MH⁺=696.

Example 577N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methylpentanamide(X)

[1715] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),3-iodobenzylamine (VI) and 4-methylpentanoic acid (IX), the titlecompound is obtained, MH⁺=531.

Example 578N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methylpentanamide(X)

[1716] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),3-iodobenzylamine (VI) and CH₃—CH₂—CH(CH₃—)—CH₂—CO—OH (IX), the titlecompound is obtained, MH⁺=531.

Example 579N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-hydroxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1717] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V),3-hydroxybenzylamine (VI) and “5-Me-PHTH” (IX), the title compound isobtained, MH⁺=568.

Example 580 tert-butyl(1S)-1-(3,5-difluorobenzyl)-3-[(3-methoxybenzyl)amino]-2-oxopropylcarbamate(XI)

[1718] tert-butyl(1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate (III, EXAMPLE1, 1 equivalent) is dissolved in isopropanol and treated with3-methoxybenzylamine (VI, 5 equivalents). The reaction is heated atreflux for 2 hours and monitored by TLC for disappearance of the ketone(III). Upon completion, the reaction is concentrated to dryness underreduced pressure and partitioned between equal parts water and ethylacetate. The organic phase is extracted, washed two additional timeswith water, then saline, then dried over anhydrous sodium sulfate,filtered and concentrated under reduced pressure. The crude material ispurified by column chromatography on silica gel to give the titlecompound.

Example 581 tert-butyl(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (XIII)

[1719]tert-butyl-(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate(XII, EXAMPLE 165, 1 equivalent) is dissolved in methanol and treatedwith 10% palladium on carbon under hydrogen (50 psi). The reaction isshaken at 20-25 degrees C. for 2 hours, filtered through a diatomaceousearthpad, and concentrated under reduced pressure to dryness. The crudematerial is purified by column chromatography on silica gel to give thetitle compound.

Example 582 Benzyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII)

[1720] A mixture of benzyl (1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate(V, 0.22 g, 0.74 mmol), 3-methoxybenzylamine (VI, 0.13 g, 0.92 mmol),and ethanol (2 mL) is stirred at reflux for 2.3 hours and then cooledand concentrated under reduced pressure. The residue ischouromatographed (silica gel; methanol/dichloromethane/ammoniumhydroxide, 4/96/trace) to give the title compound, MS m/z at(m+H)⁺=435.2.

Example 583 Benzyl(1S,2R)-1-benzyl-2-hydroxy-3-(tert-butylcarbamoyl)-3-[(3-methoxybenzyl)amino]propyl-carbamate(XXXIV)

[1721] A mixture of benzyl(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl-carbamate(VII, EXAMPLE 582, 9.00 g, 21.0 mmol), di-tert-butyl dicarbonate (5.00g, 23 mmol), sodium carbonate monohydrate (3.12 g, 25 mmol), THF (200mL), and water (100 mL) is stirred at 20-25 degrees C. for 2 hours. THFis removed under reduced pressure and the residue is partitioned betweenethyl acetate and water. The organic layer is then washed with saline,dried over anhydrous sodium sulfate, filtered, and concentrated. Columnchromatography (silica gel; methanol/dichloromethane, 1/99) gives thetitle compound, NMR (300 MHz, CDCl₃) delta 7.26, 6.79, 5.00, 4.42, 3.89,3.78, 3.44, 3.28, 2.91, 1.49; MS (ESI+) for C₃₁H₃₈N₂O₆ m/z (M+H)⁺=535.3.

Example 584 tert-Butyl(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl(3-methoxybenzyl)carbamate (XXXV)

[1722] A suspension of benzyl(1S,2R)-1-benzyl-2-hydroxy-3-(tert-butylcarbamoyl)-3-[(3-methoxybenzyl)amino]propyl-carbamate(XXXIV, EXAMPLE 583, 10.2 g, 18.6 mmol) and palladium on carbon (5%,1.00 g) in ethanol (100 mL) is shaken in a hydrogenation apparatus underhydrogen (50 psi) for 2 hours. Then the mixture is filtered throughdiatomaceous earth and concentrated. The concentrate ischromatographed.(silica gel; methanol/dichloromethane, 5/95) to give thetitle compound, NMR (CDCl₃) δ 1.50, 2.46, 2.92, 3.04, 3.42, 3.52, 3.72,3.82, 4.49, 6.83, 7.19 and 7.28; MS (ESI+) for C₂₃H₃₂N₂O₄ m/z(M+H)⁺=401.3.

Example 585 tert-butyl(2R,3S)-3-({3-cyano-5-[(dipropylamino)carbonyl]benzoyl}amino)-2-hydroxy4-phenylbutyl(3-methoxybenzyl)carbamate(XXVI)

[1723] To a mixture of 3-cyano-5-[(dipropylamino)carbonyl]benzoic acid(IX/XXXII, PREPARATION 7, 0.086 g, 0.314 mmol) and tert-butyl(2R,3S)3-amino-2-hydroxy4-phenylbutyl(3-methoxybenzyl)carbamate (XXXV,EXAMPLE 584, 0.126 g, 0.314 mmol) in dichloromethane (0.3 mL) is addeddiethylcyanophosphonate (0.062 g, 0.330 mmol) and triethylamine (0.032g, 0.316 mmol). The mixture is stirred at 20-25 degrees for 65 hours andthen partitioned between dichloromethane and saturated aqueous sodiumbicarbonate. The organic phase is separated and dried over sodiumsulfate and concentrated. The residue is chromatographed (silica gel, 20mL; methanol/dichloromethane, 5/95) to give several mixed fractions,which are combined and rechromatographed (silica gel; acetone/hexane,20/80) to give the title compound, MS (ESI+) for C₃₅H₄₈N₄O₆ M/z 657.6(M+H)⁺=657.6; (M+Na)=679.5 and (M—C₄H₉O₂)=557.5.

Example 586N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³,N³-dipropylisophthalamidehydrochloride (X)

[1724] A mixture of tert-butyl(2R,3S)-3-({3-cyano-5-[(dipropylamino)carbonyl]benzoyl}amino)-2-hydroxy-4-phenylbutyl(3-methoxybenzyl)carbamate(XXXVI, EXAMPLE 585, 0.080 g, 0.122 mmol), dichloromethane (1 mL), andmethanol saturated with hydrochloric acid (1 mL) is stirred for 8 hours,after which time the solvents are removed under reduced pressure. A fewdrops of methanol, followed by ether, gives the title compound, MS(ESI+) for C₃₃H₄₀N₄O₄ m/z (M+H)⁺=557.5.

Example 587N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide(X)

[1725] To a mixture of3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoic acid (IX,PREPARATION 6, 0.18 g, 0.616 mmol) in dry DMF (16 mL) is added EDC(0.182 g, 0.9 mmol), HOBT (0.127 g, 0.9 mmol), triethylamine (0.062 g,0.616 mol), and(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]4-phenyl-2-butanol (VIII,EXAMPLE 175, 0.185 g, 0.616 mmol). The mixture is stirred at 20-25degrees C. for 3 days. The mixture is partitioned between water andethyl acetate. The phases are separated and the organic phase is washedthree times with water. The organic phase is dried over anhydrousmagnesium sulfate, filtered and concentrated. Column chromatography(silica gel, 75 mL; methanol/methylene chloride, 10/90) gives the titlecompound, IR (diffuse reflectance) 3306, 3301, 3270, 2962, 1676, 1667,1663, 1645, 1638, 1627, 1615, 1550,1537, 1450 and 1439 cm⁻¹;NMR(CDCl₃)δ0.645, 0.968, 1.20, 1.43, 1.67, 2.8, 2.97, 3.38, 3.47, 3.73, 3.87, 4.31,6.78, 6.91, 7.23, 7.72, 7.87, 8.22 and 8.43.

Example 588 1-tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propylcarbamate(VII)

[1726] tert-Butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, EXAMPLE3, 1.75 g, 5.8 mmole) is mixed with isopropanol (30 ml). The reactionflask is charged with 3-iodobenzylamine (VI). The reaction mixture isheated to reflux for 45 minutes, HPLC analysis indicates completedisappearance of the epoxide (V). The reaction mixture is concentratedunder reduced pressure and the residue is partitioned between ethylacetate (150 ml) and aqueous hydrochloric acid (3%, 35 ml). The organicphase is separated and washed with aqueous hydrochloric acid (3%, 20ml), bicarbonate, saline and dried over sodium sulfate. Concentrationunder reduced pressure gives the title compound, M+H=535.

Example 589 1-9H-fluoren-9-ylmethyl(2R,3S)-3-(3-t-butyloxycarbonyl)amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3′-iodobenzyl)carbamatehydrochloride (XXXIV)

[1727] 1-tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propylcarbamate(VII, EXAMPLE 588, 2.5 g, 4.7 mmole) and triethylamine (0.72 ml, 5.1mmole) in THF (10 ml) are mixed. The reaction is cooled to 0 degrees andtreated with FMOC-Cl (1.2 g, 4.7 mmole) in THF (2 ml) via additionfunnel. After 15 minutes HPLC indicates complete disappearance ofstarting material. The reaction is diluted with ethyl acetate and washedwith aqueous potassium bisulfate, saturated aqueous bicarbonate, salineand dried over sodium sulfate. Concentration under reduced pressuregives crude product which is purified by flash chromatography, elutingwith ethyl acetate/hexane (20/80) followed by ethyl acetate to give thetitle compound, M+H=757.

Example 590 1-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamatehydrochloride (XXXV)

[1728] 1-9H-fluoren-9-ylmethyl(2R,3S)-3-(3-t-butyloxycarbonyl)amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3′-iodobenzyl)carbamatehydrochloride (XXXIV, EXAMPLE 589, 2.9 g) in hydrochloric acid/dioxane(4N, 10 ml). The mixture is stirred 1 hour then slowly poured intorapidly stirring ether (200 ml). The product is filtered and dried togive the title compound, M+H=657.

Example 591 1-9H-fluoren-9-ylmethyl(2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate(XXXVI)

[1729] HOBt (81 mg, 0.6 mmole) and EDC (105 mg, 0.55 mmole) are added to1-carboxy-5-piperdinylglutaramide (IX, 100 mg, 0.5 mmole) in DMF (2 ml).The acid is activated 60 minutes then treated with1-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamatehydrochloride (XXXV, EXAMPLE 590, 300 mg, 0.43 mmole) and NMM (0.19 ml,1.72 mmole). The reaction is stirred 3 hours then concentrated underreduced pressure. The residue is partitioned between ethyl acetate andsaturated aqueous bicarbonate. The organic phases are washed withaqueous potassium bisulfate, saline, dried over sodium sulfate andfinally concentrated under reduced pressure to give crude product.Purification via flash chromatography with ethyl acetate/hexane (50/50)then methanol/ethyl acetate (10/90) gives the title compound, M+H=838.

Example 5921-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamidetrifluroacetate (X)

[1730]1-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamidetrifluroacetate (XXXVI, EXAMPLE 591, 240 mg, 0.29 mmole is dissolved indiethylamine (10%, 9 ml) in methylene chloride. The reaction is stirredat 20-25 degrees overnight. The next morning the reaction isconcentrated under reduced pressure and the residue is redissolved inmethylene chloride and purified by preparative reverse phase HPLC. Theappropriate fractions are pooled and concentrated under reduced pressureand partitioned between ethyl acetate and saline. The organic phase isseparated and dried over sodium sulfate and concentrated to give thetitle compound, M+H=614.

Example 5935-(Aminosulfonyl)-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N-dipropylisophthalamide(X)

[1731] O—(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU, 0.0928 g, 0.244 mmol) is added to a mixtureof, 3-(aminosulfonyl)-5-[(dipropylamino)-carbonyl]benzoic acid (XXXIX,PREPARATION 13, 0.0800 g, 0.244 mmol) and(2R,3S)-3-amino-1-[(3-methoxybenzyl)-amino]-4-phenyl-2-butanol (VIII,EXAMPLE 175, 0.0732 g, 0.244 mmol) in dry DMF (3 mL). The mixture isstirred for 18 hours at 20-25 degrees, and then partitioned betweenethyl acetate and water. The organic phase is separated and washed withsaline, dried over anhydrous sodium sulfate, filtered and concentrated.The concentrate is column chouromatographed (silica gel;methanol/dichloromethane, 5/95) to give the title compound, MS (ESI+)for C₃₂H₄₂N₄O₆S m/z (M+H)⁺=611.5; HRMS (FAB) calculated for C₃₂H₄₂N₄O₆S+H₁=611.2903, found=611.2904.

Example 594N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-pyrrolidinylsulfonyl)isophthalamide(X)

[1732] Following the general procedure of EXAMPLE 593 and makingnon-critical variations but using3-[(dipropylamino)carbonyl]-5-(1-pyrrolidinylsulfonyl)benzoic acid(XXXIX, PREPARATION 15, the title compound is obtained, ES (ESI+) forC₃₆H48N₄O₆S m/z (M+H)⁺=665.6;HRMS (FAB) calculated for C₃₆H4₈N₄O₆S+H₁=665.3372, found=665.3393.

Example 595N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylamino)sulfonyl]-N³,N³-dipropylisophthalamide(X)

[1733] Following the general procedure of EXAMPLE 593 and makingnon-critical variations but using3-[(dipropylamino)carbonyl]-5-[(methylamino)-sulfonyl]benzoic 30 acid(XXXIX, PREPARATION 17, the title compound is obtained, MS (ESI+) forC₃₃H₄₄N₄O₆S mZ (M+H)⁺=625.5.

Example 596N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(dimethylamino)sulfonyl]-N³,N³-dipropylisophthalamide(X)

[1734] Following the general procedure of EXAMPLE 593 and makingnon-critical 5 variations but using3-[(dimethylamino)sulfonyl]-5-[(dipropylamino)carbonyl]-benzoic acid(XXXIX, PREPARATION 19), the title compound is obtained, MS (ESI+) forC₃₄H₄₆N₄O₆S m/z (M+H)⁺=639.5.

Examples 597-619

[1735] Following the general procedure of EXAMPLEs 589 through 592 butstarting with(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII,EXAMPLE 175) and using the amide forming agent (IX) of Column A, theSubstituted Amine (X) of Column B is obtained. Column A MS EX AmideForming Column B Data # Agent (IX) Substituted Amine (X) M + H 5972-methyl-3- N-{(1S,2R)-1-benzyl-2- 449 (methylsulfonyl) hydroxy-3-[(3-propanoic acid methoxybenzyl)amino]propyl}- 2-methyl-3-(methylsulfonyl)propanamide hydrochloride 598 3-(methylsulfonyl) N-{(1S,2R)-1-benzyl-2-435 propanoic acid hydroxy-3-[(3-methoxybenzyl) amino]propyl}-3-(methylsulfonyl)propanamide hydrochloride 599 2-amino-1,3-thiazole-2-amino-N-{(1S,2R)-1-benzyl- 427 4-carboxylic acid 2-hydroxy-3-[(3-hydrochloride methoxybenzyl)amino]propyl}- 1,3-thiazole-4-carboxamidedihydrochloride 600 5-(methylsulfonyl) N-{(1S,2R)-1-benzyl-2- 463pentanoic acid hydroxy-3-[(3- methoxybenzyl)amino]propyl}-5-(methylsulfonyl)pentanamide hydrochloride 601 4-anilino-4-N¹-{(1S,2R)-1-benzyl-2- 476 oxobutanoic acidhydroxy-3-[(3-methoxybenzyl) amino]propyl}-N⁴- phenylsuccinamidehydrochloride 602 (2R)-4-amino-2,3,3- (3R)-N⁴-{(1S,2R)-1-benzyl-2- 442trimethyl-4- hydroxy-3-[(3- oxobutanoic acidmethoxybenzyl)amino]propyl}- 2,2,3-trimethylbutanediamide hydrochloride603 3-[(dipropylamino) N-{(1S,2R)-1-benzyl-2- 520 sulfonyl]hydroxy-3-[(3- propanoic acid methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]- propanamide hydrochloride 6045-(dipropylamino)-5- N¹-{(1S,2R)-1-benzyl-2- 498 oxopentanoic acidhydroxy-3-[(3-methoxybenzyl) amino]propyl}-N⁵,N⁵- dipropylpentanediamidehydrochloride 605 4-oxo-4-(1-piperidinyl) N-{(1S,2R)-1-benzyl-2- 468butanoic acid hydroxy-3-[(3-methoxybenzyl) amino]propyl}-4-oxo-4-(1-piperidinyl)butanamide hydrochloride 606 4-(dipropylamino)-4-N˜1˜-{(1S,2R)-1-benzyl-2- 484 oxobutanoic acidhydroxy-3-[(3-methoxybenzyl) amino]propyl}-N⁴,N⁴- dipropylsuccinamidehydrochloride 607 5-oxo-5-(1-piperidinyl) N-{(1S,2R)-1-benzyl-2- 482pentanoic acid hydroxy-3-[(3-methoxybenzyl) amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide hydrochloride 608 5-anilino-5-N^(1-{(1S,2R)-1-benzyl-2-) 490 oxopentanoic acidhydroxy-3-[(3-methoxybenzyl) amino]propyl}-N⁵- phenylpentanediamidehydrochloride 609 3,3-dimethyl-4-oxo-4- N-{(1S,2R)-1-benzyl-2- 496(1-piperidinyl) hydroxy-3-[(3-methoxybenzyl) butanoic acidamino]propyl}-3,3-dimethyl-4- oxo-4-(1-piperidinyl) butanamidehydrochloride 610 4-(isopentylsulfonyl) N-{(1S,2R)-1-benzyl-2- 505butanoic acid hydroxy-3-[3-methoxybenzyl) amino]propyl}-4-(isopentylsulfonyl) butanamide hydrochloride 611 4-(dipropylamino)-2,2-N¹-{(1S,2R)-1-benzyl-2- 512 dimethyl-4- hydroxy-3-[(3-methoxybenzyl)oxobutanoic acid amino]propyl}-2,2-dimethyl- N⁴,N⁴-dipropylsuccinamidehydrochloride 612 4-[(dipropylamino) N-{(1S,2R)-1-benzyl-2- 534sulfonyl] hydroxy-3-[(3-methoxybenzyl) butanoic acid amino]propyl}-4-[(dipropylamino)sulfonyl] butanamide hydrochloride 6134-[(methylanilino) N-{(1S,2R)-1-benzyl-2- 540 sulfonyl]hydroxy-3-[(3-methoxybenzyl) butanoic acid amino]propyl}-4-[(methylanilino)sulfonyl]butana- mide hydrochloride 6143-[(methylanilino) N-{(1S,2R)-1-benzyl-2- 526 sulfonyl]propanoichydroxy-3-[(3-methoxybenzyl) acid amino]propyl}-3-[(methylanilino)sulfonyl]propan- amide 615 Acetic acidN-{(1S,2R)-1-benzyl-2- 343 hydroxy-3-[(3-methoxybenzyl)amino]propyl}acetamide hydrochloride 616 3-(isopentylsulfonyl)N-{(1S,2R)-1-benzyl-2- 491 propanoic acid hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3- (isopentylsulfonyl) propanamide hydrochloride 6175-oxo-5-(1-piperidinyl) N-{(1S,2R)-1-(3,5- 614 pentanoic aciddifluorobenzyl)-2-hydroxy-3- [(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl) pentanamide trifluoroacetate 6185-oxo-5-(1-piperidinyl) N-{(1S,2R)-1-benzyl-2- 578 pentanoic acidhydroxy-3-[(3-iodobenzyl) amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide trifluoroacetate 619 3-[(dipropylamino)N-{(1S,2R)-1-(3,5- 652 sulfonyl] difluorobenzyl)-2-hydroxy-3- propanoicacid [(3-iodobenzyl)amino]propyl}- 3-[(dipropylamino)sulfonyl]propanamide

Example 620N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethyl-N³,N³-dipropylisophthalamide(X)

[1736] Diethyl cyanophosphonate (0.132 mL, 0.870 mmol) is added to amixture of 3-[(dipropylamino)carbonyl]-5-ethylbenzoic acid (IX,PREPARATION 21, 0.200 g, 0.720 mmol),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII,EXAMPLE 175, 0.216 mg, 0.720 mmol), and triethylamine (0.121 mL, 0.870mmol) in dichloromethane (3 mL). The mixture was stirred for 1 hour at20-25 degrees C. Dichloromethane is then removed under reduced pressure.The residue is partitioned between ethyl acetate and water. The organicphase is separated and is washed with saline, dried over anhydroussodium sulfate, filtered and concentrated. The concentrate is columnchouromatographed (silica gel; methanol/dichloromethane, 5/95) to givethe title compound, MS (ESI+) for C₃₄H₄₅N₃O₄ m/Z (M+H)⁺=560.4; HOURMS(FAB) calculated for C₃₄H₄₅N₃O₄+H=560.3488, found=560.3487.

Example 621N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-isobutyl-N³,N³-dipropylisophthalamide

[1737] Following the general procedure of PREPARATIONS 20 and 21 andmaking non-critical variations but using isobutylboronic acid, andfollowing the general procedure of EXAMPLE 620 but using the5-isobutylisophthalic acid (IX), the title compound is obtained, MS(ESI+) for C₃₆H₄₉N₃O₄ M/z (M+H)⁺=588.6;HRMS (FAB) calculated forC₃₆H₄₉N₃O₄+H₁=588.3801, found=588.3810.

Example 622N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-tert-butyl-N³,N³-dipropylisophthalamide

[1738] Following the general procedure of PREPARATIONS 20 and 21 andmaking non-critical variations but using tert-butylboronic acid, andfollowing the general procedure of EXAMPLE 620 but using thetert-butylphthalic acid (IX), the title compound is obtained, MS (ESI+)for C₃₆H₄₉N₃O₄ m/z (M+H)⁺=588.5;HRMS (FAB) calculated for C₃₆ H₄₉N₃O₄+H₁=588.3801, found=588.3791.

Example 623N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³-propylisophthalamide(X)

[1739] Following the general procedure of EXAMPLE 586 and makingnon-critical variations, but using tert-butyl(2R,3S)-3-({3-cyano-5-[(propylamino)carbonyl]benzoyl}amino)-2-hydroxy-4-phenylbutyl(3-methoybenzyl)carbamate(XXXVI) the title compound is obtained, M+H=515.1.

ExampleS 624-628

[1740] Following the general procedure of EXAMPLE 587 and makingnon-critical variations, but using the appropriate amines (VIII) andamide forming agents (IX), for example PREPARATIONS 6 and 19, the titledcompounds are obtained. EXAM- M + PLE Substituted Amine (X) H = 624N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3- 611.0methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5- benzenetricarboxamide625 N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3- 603.0methoxybenzyl)amino]propyl}-N³,N³-dimethyl-N⁵,N⁵-dipropyl-1,3,5-benzenetricarboxamide 626N¹-[(1S,2R)-3-amino-1-benzyl-2-hydroxypropyl]- 455.1N³,N³-dipropyl-1,3,5-benzenetricarboxamide 627N¹-[(1S,2R)-1-benzyl-2-hydroxy-3- 525.6(isopentylamino)propyl]-N³,N³-dipropyl-1,3,5- benzenetricarboxamide 628N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3- 533.1methoxybenzyl)amino]propyl}-N³-propyl-1,3,5- benzenetricarboxamide

Example 629N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-3-[butyryl(propyl)amino]-5-methylbenzamide(X)

[1741] Following the procedure of EXAMPLE 570 and making non-criticalvariations, diethyl cyanophosphonate (0.0760 mL, 0.550 mmol) is added toa mixture of 3-[butyryl(propyl)amino]-5-methylbenzoic acid (IX, 0.120 g,0.460 mmol),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII,0.137 g, 0.460 mmol), and triethylamine (0.0760 mL, 0.550 mmol) indichloromethane (5 mL). The mixture is stirred for 1 hour at 20-25degrees C. Dichloromethane is then removed under reduced pressure. Theresidue is partitioned between ethyl acetate and water. The organic isseparated, is washed with saline, dried over anhydrous sodium sulfate,filtered and concentrated. The concentrate is column chromatographed(silica gel; methanol/dichloromethane, 5/95) to give the title compound,NMR (400 MHz, CDCl₃) δ 7.09, 4.15, 3.80, 3.79, 3.60, 3.02, 2.84, 2.36,1.94, 1.56, 1.49, 0.87 and 0.81; MS (ESI+) for C₃₃H₄₃N₃O₄ m/z(M+H)⁺=546.3; HRMS (FAB) calculated for C₃₃H₄₃N₃O₄+H=546.3331,found=546.3331.

Example 630N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyll}-1-propyl-1H-indole-6-carboxamide(X)

[1742] Following the general procedure of EXAMPLE 539 and makingnon-critical variations, the title compound is obtained, IR (diffusereflectance) 3330, 3314, 2960, 2952, 2931, 2873, 1621, 1599, 1525, 1499,1467, 1353, 1283, 1253 and 786 cm⁻¹.

Example 631N-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide(-X)

[1743] Following the general procedure of EXAMPLE 539 and makingnon-critical variations, the title compound is obtained, IR (diffusereflectance) 3289, 1627, 1621, 1595, 1531, 1525, 1520, 1507, 1466, 1458,1450, 1349, 1317, 1252 and 1117 cm⁻¹.

Examples 633-708

[1744] Following the general procedures of CHART A as well asPREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thesubstituted amines (X) of

ExampleS 633-708 are obtained.

[1745] EXAMPLE Substituted Amine (X) MH⁺ = 633N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide580 634 N¹-[(1S,R)-3-[(3-aminobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide567 635N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}octanamide559 636 N³-[(1S,2R)-1-(3,5-difluoro- 635benzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide637 N¹-[(1S,2R)-1-(3,5-difluoro- 648benzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-5-methy-N³,N³-dipropylisophthalamide638 N¹-((1S,2R)-1-(3,5-difluoro- 594benzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide639 N¹-{(1S,2R)-1-(3,5-difluoro- 578benzyl)-3-[(1R)-3,4-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide640N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methylbenzamide551 641N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1H-isoindol-3-ylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide577 642 N¹-((1S,2R)-1-(3,5-difluoro- 600benzyl)-2-hydroxy-3-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide643N¹,N¹-diallyl-5-chloro-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}isophthalamide597 644 5-chloro-N¹-{(1S,2R)-1-(3,5-difluoro- 633benzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-bis(2-methoxyethyl)isophthalamide645 N³-{(1S,2R)-1-(3,5-difluoro- 593benzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide646N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide580 647 N¹-((1S,2R)-1-(3,5-difluoro- 595benzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide648 N¹-((1S,2R)-1-(3,5-difluoro- 570benzyl)-3-{[(4,5-dimethyl-2-furyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide649N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide606 650N¹-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide502 651N¹-[(1S,2R)-3-[(cycloproylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide516 652N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide630 653N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide529 654 N¹-{(1S,2R)-1-(3,5-difluoro- 546benzyl)-2-hydroxy-3-[(tetrahydro-2-furanylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide655 N³-{(1S,2R)-1-(3,5-difluoro- 565benzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide656N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-oxo-3-azepanyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide573 657 N¹-((1S,2R)-1-(3,5-difluoro- 556benzyl)-2-hydroxy-3-{[(3-methyl-2-furyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide658 N¹-((1S,2R)-1-(3,5-difluoro- 546benzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide659 5-chloro-N¹-{(1S,2R)-1-(3,5-difluoro- 593benzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-di(2-propynyl)isophthalamide660N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropenylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide592 661N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-5-methyl-N³,³-dipropylisophthalamide548 662 N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(hexylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide546 663 N-{(1S,2R)-1-(3,5-difluoro- 633benzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzamide664 methyl 4-({[(2R,3S)-4-(3,5-difluoro- 610phenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)benzoate665N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide520 666N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-isoxazolylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide543 667 (1R,2R)-N¹-{(1S,2R)-1-(3,5-difluoro- 628benzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide668 N³-((1S,2R)-1-(3,5-difluoro- 533benzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide669N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide582 670N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide594 6714-(butyrylamino)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}benzamide622 672N¹-[(1S,2R)-3-[(3-amino-3-oxopropyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide533 673N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide1-oxide 555 674N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide688 675 N¹-{(1S,2R)-1-(3,5-difluoro- 572benzyl)-2-hydroxy-3-[(7-oxabicyclo[2.2.1]hept-2-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide676N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide576 677 N¹-((1S,2R)-1-(3,5-difluoro- 573benzyl)-2-hydroxy-3-{[(2-methyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide678 N¹-((1S,2R)-1-(3,5-difluoro- 587benzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide679N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3R)-2-oxoazepanyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide573 680N¹-[(1S,2R)-3-(cyclobutylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide516 681N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-ethynyl-N³,N³-dipropylisophthalamide528 682N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide590 683N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(5-hexynylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide542 684 N³-((1S,2R)-1-(3,5-difluoro- 543benzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide685N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide532 686 N¹-((1S,2R)-1-(3,5-difluoro- 570benzyl)-3-{[1-(2-furyl)-1-methylethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide687 N¹-((1S,2R)-1-(3,5-difluoro- 599benzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide688 N¹-((1S,2R)-1-(3,5-difluoro- 615benzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide689N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide554 690N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide516 691N¹-((1S,2R)-1-benzyl-3-{[2-(2-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide551 692N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}propyl)-N³,N³-dipropylisophthalamide537 693N¹-{(1S,2R)-1-benzyl-3-{(cyclohexylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide508 694N¹-[(1S,2R)-1-benzyl-3-(cyclopropylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide452 695N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-oxo-3-azepanyl)amino]propyl}-N³,N³-dipropylisophthalamide523 696N-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-(butylsulfonyl)benzamide531 697N¹-[(1S,2R)-1-benzyl-3-({2-[(2-ethylhexyl)oxy]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide568 698 N¹-((1S,2R)-1-benzyl-2-hy- 544droxy-3-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-dipropylisophthalamide699N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[1-(4-hydroxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide532 700N¹-[(1S,2R)-1-benzyl-3-(cylcoheptylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide508 701N¹-{(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-2-ylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide578 702N¹-{(1S,2R)-1-benzyl-3-[(2-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide520 703N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(dimethylamino)benzamide484 704N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-naphthamide491 705 N¹-[(1S,2R)-1-benzyl-3-({2-[({5-[(dimethyl- 609amino)methyl]-2-furyl}methyl)sulfanyl]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide706N¹-[(1S,2R)-1-benzyl-3-({2-[(2-chloro-6-fluorobenzyl)sulfanyl]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide615 707 N¹-[(1S,2R)-3-[([1,1′-bi- 628phenyl]-4-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide708N¹-[(1S,2R)-1-(3,5-diflorobenzyl)-2-hydroxy-3-(1-naphthylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide588

Examples 709-737

[1746] Following the general procedure of CHART D and EXAMPLEs 165-169and making non-critical variations and using the appropriate reagents,the substituted amines (X) of EXAMPLES 709-737 are obtained. EXAMPLESubstituted Amine (X) MH⁺ 709 N¹-{(1S,2R)-1-(3,5-difluoro- 542benzyl)-2-hydroxy-3-[(1H-imidazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide710 N¹-((1S,2R)-1-(3,5-difluoro- 618benzyl)-2-hydroxy-3-{[(2-phenyl-1H-imidazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide711 N¹-((1S,2R)-1-(3,5-difluoro- 556benzyl)-2-hydroxy-3-{[(1-methyl-1H-imidazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide712 N¹-[(1S,2R)-3-{[(2-butyl-4-chloro-1H-imi- 633dazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide713 N¹-[(1S,2R)-3-{[(6-chloro- 633imidazo[2,1-b][1,3]thiazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide714 N¹-((1S,2R)-1-(3,5-difluoro- 606benzyl)-2-hydroxy-3-{[(1-methyl-1H-benzimidazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide715 N¹-((1S,2R)-1-(3,5-difluoro- 618benzyl)-2-hydroxy-3-{[(2-hydroxy-1-naphthyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide716 N¹-((1S,2R)-1-(3,5-difluoro- 620benzyl)-2-hydroxy-3-{[(4-oxo-4H-chouromen-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide717 N¹-((1S,2R)-1-(3,5-difluoro- 662benzyl)-3-{[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 718 N¹-[(1S,2R)-3-({[5-cyano-6-(methyl- 624sulfanyl)-2-pyridinyl]methyl}amino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide719 [5-({[(2R,3S)-4-(3,5-difluoro- 614phenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl-2-furyl]methylacetate 720N¹-[(1S,2R)-3-[(1-benzofuran-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide592 721 methyl 4-({[(2R,3S)-4-(3,5-difluoro- 613phenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1-methyl-1H-pyr-role-2-carboxylate 722 N¹-[(1S,2R)-1-(3,5-difluoro- 681benzyl)-2-hydroxy-3-({[1-(phenylsulfonyl)-1H-pyrrol-2-yl]methyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide723 N¹-((1S,2R)-1-(3,5-difluoro- 555benzyl)-2-hydroxy-3-{[(1-methy-1H-pyrrol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide724 N¹-[(1S,2R)-3-{[(4-chloro-1-meth- 591yl-1H-pyrazol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide725 N¹-((1S,2R)-1-(3,5-difluoro- 646benzyl)-3-{[(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide726 N¹-[(1S,2R)-3-{[(5-chloro-3-meth- 667yl-1-phenyl-1H-pyrazol-4-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide727 N¹((1S,2R)-1-(3,5-difluoro- 618benzyl)-2-hydroxy-3-{[(3-phenyl-1H-pyrazol-4-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide728 N¹-[(1S,2R)-3-{[(5-chloro-2-thie- 593nyl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide729 N¹-((1S,2R)-1-(3,5-difluoro- 650benzyl)-2-hydroxy-3-{[(3-phenoxy-2-thienyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide730N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-quinolinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide603 731N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-quinolinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide603 732 N¹-((1S,2R)-1-(3,5-difluoro- 605benzyl)-2-hydroxy-3-{[(1-methyl-1H-indol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide733 N¹-[(1S,2R)-3-{[(1-ben- 681zyl-1H-indol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide734 N¹-((1S,2R)-1-(3,5-difluoro- 605benzyl)-2-hydroxy-3-{[(1-methyl-1H-indol-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide735 N¹-{(1S,2R)-1-(3,5-difluoro-benzyl)-2-hy- 745droxy-3-[({1-[(4-methylphenyl)sulfonyl]-1H-indol-3-yl}methyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide736 N¹-[(1S,2R)-3-{[(2-butyl-1H-imi- 598dazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide737 methyl 3-({[(2R,3S)-4-(3,5-difluoro- 649phenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1H-indole-6-carboxylate

Example 7383-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[butyl(butyryl)amino]benzyldiethyl phosphate (X)

[1747] Following the general procedure of CHART L and EXAMPLE 620 andmaking non-critical variations, the title compound is obained, HRMS(FAB)=712.3749.

Example 739N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(cyanomethyl)-N³,N³-dipropylisophthalamide(X)

[1748] Step 1.

[1749] A mixture of diethyl 1,3,5-benzenetricarboxylate (5.2 g) andborane methylsulfide complex (6.1 g) is stirred in THF (150 mL) at 20-25degrees C. overnight. The mixture is then treated with methanol,concentrated to dryness, and chouromatographed (silica gel) to givediethyl 5-(hydroxymethyl)isophthalate. Diethyl5-(hydroxymethyl)isophthalate (3.4 g) is hydroyzed in ethanol and waterwith lithium hydroxide monohydrate (0.57 g) at 20-25 degrees C. for 3.5hours at which time the solvents are removed under reduced pressure.Water (100 mL) is added and the mixture is acidified to pH=4 withconcentrated hydrochloric acid. The mixture is extracted with ethylacetate and dried over magnesium sulfate, filtered, and concentrated togive 3-(ethoxycarbonyl)-5-(hydroxymethyl)benzoic acid, high resolutionMS MH+=225.0769. 3-(Ethoxycarbonyl)-5-(hydroxymethyl)benzoic acid (2.3g), EDC (3.0 g), 1-HOBT (2.1 g), diisopropylethylamine (2.7 mL),dipropyl amine (2.8 mL), and DMF (50 mL) are stirred at 20-25 degrees C.overnight. The mixture is then partitioned between ethyl acetate, water,and saline. The organic phase is separated and dried over magnesiumsulfate, filtered, and concentrated. Chromatography (silica gel) givesethyl 3-[(dipropylamino)carbonyl]-5-(hydroxymethyl)benzoate, NMR (CDCl₃)δ 0.77, 1.0, 1.4, 1.6, 1.7, 3.2, 3.5, 4.4, 4.8, 7.6, 8.0 and 8.1.

[1750] Step 2.

[1751] A mixture of ethyl3-[(dipropylamino)carbonyl]-5-(hydroxymethyl)benzoate (1.5 g) andphosphorous tribromide (0.95 mL) is stirred in dichloromethane (10 mL)and heated at 50 degrees C. for 4 hours and then cooled and partitionedbetween dichloromethane and water. The organic phase is separated andwashed with aqueous sodium bicarbonate and then dried over magnesiumsulfate and taken to dryness to give ethyl3-(bromomethyl)-5-[(dipropylamino)carbonyl]benzoate, high resolution MSMH+=370.1020. Ethyl 3-(bromomethyl)-5-[(dipropylamino)carbonyl]benzoate(1.4 g) and sodium cyanide (0.2 g) are stirred in dry DMSO (25 mL) at20-25 degrees C. for 3.5 hours and the mixture is then partitionedbetween ethyl acetate, water and saline. The organic layer is separatedand dried over magnesium sulfate and taken to dryness under reducedpressure to give ethyl3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoate. Ethyl3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoate (0.6 g) ishydrolyzed with lithium hydroxide monohydrate (0.1 g) in ethanol andwater at 20-25 degrees C. overnight and then added to water (50 mL). ThepH is adjusted to 4 using concentrated hydrochloric acid and the mixtureis partitioned between ethyl acetate, water, and saline. The organicphase is separated and dried over magnesium sulfate and taken to drynessunder reduced pressure to give3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoic acid, MS M+H=287.2.

[1752] Step 3.

[1753] A mixture of 3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoicacid (IX, 0.13 g),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII,0.14 g), HATU (0.17 g), and dichloromethane (10 mL) is stirred at 40degrees C. overnight. After cooling, the mixture is washed with waterand the organic phase is separated and dried over magnesium sulfate andtaken to dryness under reduced pressure. Chromatography (silica gel)gives the title compound, M+H=571.2.

Example 740N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(hydroxymethyl)-N³,N³-dipropylisophthalamide(X)

[1754] Following the procedure of CHART P and EXAMPLE 739 and makingnon-critical variations but using3-[(dipropylamino)carbonyl]-5-(hydroxymethyl)benzoic acid (IX) and(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]4-phenyl-2-butanol (VIII), thetitle compound is obtained, HRMS (FAB)=615.3571.

Example 741N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide(X)

[1755] Step 1:

[1756] A mixture of methyl 3-bromo-5-[(dipropylamino)carbonyl]benzoate(XXI, 200 mg, 0.58 mmol), PdCl₂(Ph₃P)₂ (16 mg, 0.03 mol %) and copper(I) iodide (6 mg, 0.05 mol %/o) in triethylamine (1.2 mL) is heated toreflux. (Trimethylsilyl) acetylene (100 microliter, 0.7 mmol) is added,and the mixture stirred for 3 hours, cooled to 20-25 degrees, dilutedwith water (20 mL), and extracted with chloroform (3×15 mL). Thecombined organic extracts are washed with saline (20 mL), dried oversodium sulfate and concentrated under reduced pressure to give methyl3-[(dipropylamino)carbonyl]-5-ethynylbenzoate (XXXII, 185.5 mg), NMR(300 MHz, CDCl₃): δ 7.95, 7.75, 7.43, 3.74, 3.25, 2.95, 1.49, 1.34,0.79, 0.56 and 0.06.

[1757] Step 2:

[1758] To a stirred mixture of the protected methyl3-[(dipropylamino)carbonyl]-5-ethynylbenzoate (XXXII, Step 1, 185.3 mg,0.49 mmol) in methanol (2.5 mL) is added a mixture of potassiumhydroxide (2.9 mL of a 1 M mixture in water, 2.9 mmol). The reactionmixture is stirred for 4 hours diluted with chloroform (40 mL), thephases are separated and the organic phase is concentrated under reducedpressure to give 3-[(dipropylamino)carbonyl]-5-ethynylbenzoic acid, NMR(300 MHz, CDCl₃): δ 8.22, 8.05, 7.71, 3.48, 3.17, 3.16, 1.71, 1.55, 1.00and 0.78.

[1759] Step 3:

[1760] To a stirred mixture of3-[(dipropylamino)carbonyl]-5-ethynylbenzoic acid (70 mg, 0.24 mmol) inDMF (2.5 mL) is added(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII, 81 mg, 0.24 mmol), HOBt (36 mg, 0.26 mmol) anddiisopropylethylamine (170 microliter, 0.96 mmol). To this reactionmixture is added EDC (51 mg, 0.26 mmol) and the reaction mixture isstirred overnight. The reaction mixture is diluted with ethyl acetate(30 mL), washed with water (3×50 mL), hydrochloric acid (1 N, 30 mL),saturated sodium bicarbonate (30 mL), saline (30 mL), dried over sodiumsulfate and concentrated under reduced pressure. Purification by flashchromatography (silica, ethyl acetate to methanol/chloroform, 1/10)gives the title compound, IR (KBr): 3276, 2956, 2921, 1610, 1450 and1264 cm⁻¹; ESI-MS (m/z) [M+H]⁺=556.

Example 742N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropyl-5-prop-1-ynylisophthalamide(X)

[1761] Following the general procedure of EXAMPLE 741 and makingnon-critical variations but using propyne in place of (trimethylsilyl)acetylene and using(2R,3S)-3-amino-1-[(3-iodobenzyl)amino]4-phenyl-2-butanoldihydrochloride (VIII) in place of(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]4-phenyl-2-butanoldihydrochloride (V1H), the title compound is obtained, IR (ATR): 3305,2930, 2872, 1613 and 1537 cm⁻¹; ESI-MS (m/z) [M+H]⁺=666.

Example 743N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-ethynyl-N³,N³-dipropylisophthalamide(X)

[1762] Step 1:

[1763] A mixture of tert-butyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V, 2.3 g, 8.7 mmol) and3-(trifluoromethyl)benzylamine (VI, 1.9 mL, 13.1 mmol) in 2-propanol (70mL) is heated at reflux for 4 hours. The reaction mixture is cooled to20-25 degrees and concentrated under reduced pressure to give tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propylcarbamate(VII, 3.1 g) as a solid, ESI-MS (m/z) [M+H]⁺=439.

[1764] Step 2:

[1765] A mixture of tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propylcarbamate(VII, step 1, 2.5 g, 5.7 mmol) and hydrochloric acid (29 mL of a 4.0 Mmixture in dioxane, 114 mmol) is stirred at 20-25 degrees. A precipitateforms and is collected by filtration, washed with ether, and dried underreduced pressure to give(2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanoldihydrochloride (VIII, 2.13 g), ESI-MS (m/z) [M+]⁺=339.

[1766] Step 3:

[1767] A mixture of 3-[(dipropylamino)carbonyl]-5-ethynylbenzoic acid(IX, 231 mg, 0.8 mmol),(2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanoldihydrochloride (VIII, Step 2,493.5 mg, 1.2 mmol) HOBt (162 mg, 1.2mmol), and diisopropylethylamine (832 Micro Liter, 4.8 mmol) is stirredin methylene chloride (4 mL) for 15 minutes EDC (206 mg, 1.2 mmol) isadded and the reaction mixture is stirred overnight. The reactionmixture is diluted with water, and extracted with methylene chloride(3×25 mL). The organic phase is washed with hydrochloric acid (1N, 25mL), saturated sodium bicarbonate (25 mL), saline dried over sodiumsulfate and concentrated under reduced pressure. Purification by flashcolumn chromatography (silica, 100% ethyl acetate tomethanol/chloroform, 1/9) gives title compound, IR (ATR): 3302, 2963,2932 and 1615 cm⁻¹; MS (m/z) [M+H]⁺=549.

Example 744N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide(X)

[1768] Following the general procedure of EXAMPLE 744 and makingnon-critical variations but using 3-iodobenzylamine hydrochloride salt(VI), the title compound is obtained, IR (ATR) 3295, 2960, 2927 and 1616cm⁻¹, APCI-MS (m/z) [M+H]⁼652.

Example 745N¹-{(1S,2R)-1-benzyl-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide(X)

[1769] Following the general procedure of EXAMPLE 744 and makingnon-critical variations but using 3-fluorobenzylamine (VI), the titlecompound is obtained, IR (ATR): 3217, 2961, 2918 and 1615 cm⁻¹; APCI-MS(m/z) [M+H]⁺=544.

Example 746N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(8-quinolinyl)isophthalamide(X)

[1770] Step 1:

[1771] A mixture of methyl-3-bromo-5-[(dipropylamino)carbonyl]benzoate(XLVIII, 200 mg, 0.58 mmol), 8-quinolineboronic acid (200.6 mg, 1.2mmol), sodium carbonate (870 Micro Liter of a 2 M mixture in water, 1.74mmol) in toluene (6 mL) is degassed under reduced pressure for 15minutes and purged with argon. Palladium tetrakis(triphenylphosphine)(139 mg, 0.12 nmmol) is added and the reaction mixture is degassed underreduced pressure for 15 minutes and purged with argon. The reactionmixture is heated at reflux overnight, cooled to 20-25 degrees C. anddiluted with chloroform. The organic phase is separated and washed withwater (3×50 mL), and saline, dried over sodium sulfate and concentratedunder reduced pressure. Purification by flash column chromatography(silica, ethyl acetate/hexanes, 1.3/1) gives methyl3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoate (XLIX, 176 mg), NMR(300 MHz, CDCl₃): delta 8.91, 8.42, 8.21, 8.09, 7.95, 7.86, 7.77, 7.64,3.94, 3.49, 3.34, 1.64, 0.99 and 0.84.

[1772] Step 2:

[1773] To a mixture of methyl3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoate (XLIX step 1, 175.5mg, 0.45 mmol) in methanol (2 mL) is added lithium hydroxide (32.3 mg,1.4 mmol) and water (500 microliter). After stirring overnight, thereaction mixture is partitioned between ethyl acetate (10 mL) and water(10 mL). The aqueous phase is separated and acidified with hydrochloricacid (1N), and extracted with chloroform (3×40 mL). The organic phase iswashed with saline, dried (sodium sulfate) and concentrated underreduced pressure to give3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoic acid (IX-L, 130 mg),NMR (300 MHz, CD₃OD) δ 6 8.84, 8.39, 8.35, 8.05, 7.96, 7.90, 7.87, 7.79,7.68, 3.50, 3.37, 1.76-1.61, 0.99 and 0.84.

[1774] Step 3:

[1775] A mixture of 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoicacid (IX-L, Step 2,130 mg, 0.35 mmol),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII, 117 mg, 0.35 mmol), HOBt (70 mg, 0.52 mmol) anddiisopropylethylamine (241 microliter, 1.4 mmol) in methylene chloride(2 mL) is stirred for 15 minutes EDC (89 mg, 0.52 mmol) is added and thereaction mixture is stirred overnight. The reaction mixture is dilutedwith water and extracted with methylene chloride (3×25 mL). The organicphase is washed with hydrochloric acid (1N, 25 mL), saturated sodiumbicarbonate (25 mL), saline, dried (sodium sulfate), and concentratedunder reduced pressure. Purification by flash column chromatography(silica; methanol/chloroform, 1/9) gives the title compound, IR (NaCl):3301, 2916, 2365 and 1613 cm-; APCI-MS (m/z) [M+H]⁺=659.

Example 747N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-methoxy-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamidehydrochloride (X)

[1776] Step 1:

[1777] A mixture of 4-methoxyphenyl boronic acid (463 mg, 3.05 mmol),3-bromo-5-[(dipropylamino)carbonyl]benzoic acid (XLVIII, 1.02 g, 3.05mmol), and potassium phosphate (1.29 g, 6.10 mmol) in1,2-dimethoxyethane (10 mL) and water (5 mL) is degassed with argon for15 minutes Bis(triphenylphosphine)palladium (II) chloride (21 mg, 0.03mmol) is added, the reaction mixture is degassed again with argon, andheated at 85 degrees C. overnight. The reaction mixture is cooled to20-25 degrees C., and passed through a plug of diatomaceous earth.

[1778] The filtrate is acidified to pH=4 with hydrochloric acid (IN) andextracted with ethyl acetate. The organic phase is washed with water andsaline and dried (magnesium sulfate). The product is purified by flashcolumn chromatography (silica gel; ethyl acetate/acetic acid, 99/1) togive 5-[(dipropylamino)carbonyl]-4′-methoxy[1,1′-biphenyl]-3-carboxylicacid (IX-L, 667 mg), ESI-MS (m/z) [M +H]⁺356.

[1779] Step 2:

[1780] A mixture of5-[(dipropylamino)carbonyl]-4′-methoxy[1,1′-biphenyl]-3-carboxylic acid(IX-L, step 1, 316 mg, 0.89 mmol),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII, 332 mg, 0.89 mmol), HOBt (181 mg, 1.34 mmol), andN-methylmorpholine (0.37 g, 3.56 mmol) in methylene chloride (8 mL) anddimethylformamide (2 mL) is stirred at 20-25 degrees for 15 minutes EDC(257 mg, 1.34 mmol) is added and the reaction mixture is stirred for 4.5hours. The reaction mixture is partitioned between methylene chlorideand water. The organic phase is washed with hydrochloric acid (1N),water, and saline, dried (magnesium sulfate), and concentrated. Theconcentrate is dissolved in a minimum of methanol, treated withhydrochloric acid (3 mL of a 1.0 M mixture in ether, 3 mmol), andstirred for 10 minutes. More ether is added to precipitate the rest ofthe product. The precipitate is collected by filtration and dried in thevacuum oven at 50 degrees C. to give the title compound, mp=205-209degrees C.; IR (ATR): 2964 and 1649 cm⁻¹; APCI-MS (m/z) [M+H]⁺=638.

Example 748N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamidehydrochloride (X)

[1781] Step 1:

[1782] A mixture of tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V, 500 mg,1.67 mmol) and 3-methoxybenzylamine (VI, 0.34g, 2.51 mmol) in 2-propanol(3 mL) is heated at reflux overnight, allowed to cool to 20-25 degreesC., and concentrated under reduced pressure. The residue is crystallizedfrom ethyl acetate/hexanes and collected by filtration to affordtert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII, 575 mg) as a solid: ESI-MS (m/z): 437 [M+H]⁺.

[1783] Step 2:

[1784] A mixture of tert-butyl(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII, Step 1, 535 mg, 1.23 mmol) in methanol (2 mL) is treated withhydrochloric acid (3.2 mL of a 1.0 M mixture in ether, 3.2 mmol), andstirred at 20-25 degrees C. for 30 minutes Ether is added until aprecipitate formed. The precipitate is collected by filtration is(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoldihydrochloride (VIII).

[1785] Step 3:

[1786] A mixture of5-[(dipropylamino)carbonyl][1,1′-biphenyl]-3-carboxylic acid (IX, 188mg, 0.56 mmol),(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoldihydrochloride (VIII, Step 2, 230 mg, 0.56 mmol), HOBt (114 mg, 0.84mmol), and N-methylmorpholine (0.23 g, 2.24 mmol) in methylene chloride(6 mL) and dimethylformamide (1 mL) is stirred at 20-25 degrees C. for15 minutes EDC (161 mg, 0.84 mmol) is added and the reaction mixture isstirred at 20-25 degrees C. overnight. The reaction mixture is washedwith water, 1N hydrochloric acid, water, and saline, dried (sodiumsulfate), and concentrated under reduced pressure to give the titlecompound, mp 230-233degrees C.; IR (ATR): 2965, 1651, 1596 and 1267cm⁻¹; ESI-MS (m/z) [M+H]⁺=644.

Example 749N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamidehydrochloride (X)

[1787] Following the general procedure of EXAMPLE 748 and makingnon-critical variations but using(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII) in place of(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoldihydrochloride (VIII), the title compound is obtained, mp=214-219degrees C.; IR (KBr): 3227, 2961, 1632 and 1605 cm¹; ESI-MS (m/z) [M+H]⁺=608.

Example 750N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide(X)

[1788] Step 1:

[1789] A flask is charged with1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium 1:1 complex (37mg, 0.05 mmol), potassium acetate (492 mg, 4.5 mmol) andbis(pinacolato)diboron (408 mg, 1.6 mmol) and is degassed under reducedpressure for 15 min and purged with argon. To this mixture is added amixture of methyl-3-bromo-5-[(dipropylamino)carbonyl]benzoate (XXI, 500mg, 1.5 nmmol) in anhydrous dimethyl sulfoxide (9 mL) and the reactionmixture is stirred at 80 degrees C for 4 hours. The reaction mixture iscooled to 20-25 degrees C., diluted with toluene (50 mL), washed withwater (3×150 mL), saline, dried (magnesium sulfate), and concentratedunder reduced pressure to give methyl3-[(dipropylamino)carbonyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate,ESI-MS (m/z) [M +H]⁺=390.

[1790] Step 2:

[1791] A mixture of methyl3-[(dipropylamino)carbonyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate(Step 1, 534 mg, 1.4 mmol), 4-bromobenzenedimethyl-sulfonamide (363 mg,1.4 mmol), and sodium carbonate (2 mL of a 2 M mixture in water, 4.1mmol) in toluene (10 mL) is degassed under reduced pressure for 15minutes and then purged with argon. Palladiumtetrakis(triphenylphosphine) (40 mg, 0.025 mmol) is added and thereaction mixture is degassed under reduced pressure for 15 minutes andthen purged with argon. The reaction mixture is heated at reflux for 4hours, cooled to 20-25 degrees C., filtered through a plug ofdiatomaceous earth and sodium sulfate, and the filtrate is concentratedunder reduced pressure. Purification by flash column chromatography(silica; ethyl acetate/hexanes, 1/1) gives methyl4′-[(dimethylamino)sulfonyl]-5-[(dipropylamino)carbonyl][1,1′-biphenyl]-3-carboxylate(XXXVIII), ESI-MS (m/z) [M +H]⁺=447.

[1792] Step 3:

[1793] A mixture of methyl4′-[(dimethylamino)sulfonyl]-5-[(dipropylamino)carbonyl][1,1′-biphenyl]-3-carboxylate(XXXVIII, step 2, 555 mg, 1.24 mmol) in methanol (6 mL) and sodiumhydroxide (2 mL of a 6.0 M mixture in water, 12 mmol) is stirred at20-25 degrees C. for 4 hours. The reaction mixture is partitionedbetween ethyl acetate (40 mL) and water (40 mL). The aqueous phase isacidified to pH=4 with hydrochloric acid (1N), extracted with ether(3×100 mL), and the combined organic phases are concentrated underreduced pressure to give methyl4′-[(dimethylamino)sulfonyl]-5-[(dipropylamino)carbonyl][1,1′-biphenyl]-3-carboxylic acid (IX-XXXIX), NMR (300 MHz, CDCl₃): δ8.37, 8.12, 7.89, 7.80, 3.51, 3.22, 2.76, 1.74, 1.59, 1.02 and 0.79.

[1794] Step 4:

[1795] A mixture of the acid (IX-XXXIX, Step 3, 150 mg, 0.35 mmol),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII, 129 mg, 0.35 mmol) HOBt (47 mg, 0.35 mmol), andN-methylmorpholine (122 μL, 1.1 mmol) is stirred in methylene chloride(4 mL) for 15 minutes EDC (107 mg, 0.62 mmol) is added and the reactionmixture is stirred overnight. The reaction mixture is diluted withwater, and extracted with methylene chloride (3×25 mL). The organicphase is washed with hydrochloric acid (1N, 25 mL), saturated sodiumbicarbonate (25 mL), saline, dried (sodium sulfate), and concentratedunder reduced pressure. Purification by flash column chromatography(silica; 100% ethyl acetate to methano/chloroform, 1/9) gives the titlecompound, IR (ATR): 2932, 2837 and 1593 cm⁻; APCI-MS (m/z) [M+H]⁺=715.

Example 751N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide(X)

[1796] Following the general procedure of EXAMPLE 750 and makingnon-critical variations but using2R,3S)-3-amino-1-[(3-iodobenzyl)amino]4-phenyl-2-butanol dihydrochloride(VIII), the title compound is obtained, IR (ATR): 3303, 2930, 2872 and1614 cm⁻¹; APCI-MS (m/z) [M+H]⁺=811.

Example 752N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(3-thienyl)isophthalamidehydrochloride (X)

[1797] Step 1:

[1798] To an ice-cold mixture of methyl3-amino-5-[(dipropylamino)carbonyl]benzoate (XLVIII, 1.0 g, 3.60 mmol)in aqueous hydrogen tetrafluoroborate (48% wt. in H₂O, 12.9 mmol) isadded a cold mixture of aqueous sodium nitrite (0.25 g, 3.60 mmol)dropwise. The mixture is stirred for 10 min and then extracted withethyl acetate. The organic phase is washed with water, dried overmagnesium sulfate, filtered, and concentrated under reduced pressure togive a diazonium salt which is used without further purification, NMR(500 MHz, CD₃OD): δ9.26, 8.86, 8.71, 4.03, 3.50, 3.22, 1.75, 1.60, 1.01and 0.79.

[1799] Step 2:

[1800] To a mixture of thiophene-3-boronic acid (1.0 g, 7.82 mmol) inmethanol is added a concentrated aqueous mixture of potassium hydrogendifluoride (2.01 g, 25.8 mmol) dropwise. The reaction mixture is stirredfor 10 minutes and concentrated under reduced pressure. The resultingsolid is extracted with acetone and concentrated under reduced pressuregives crude material, which is recrystallized from acetone/ether to givepotassium trifluoro(3-thienyl)borate salt, ESI-MS (m/z) [M+H]⁺=151.

[1801] Step 3:

[1802] A mixture of potassium trifluoro(3-thienyl)borate salt (step 2,0.69 g, 1.82 mmol), diazonium salt from (XLVIII, step 1, 0.42 g, 2.19mmol), and lead acetate (0.02 g, 0.09 mmol) in the dark is purged withargon for 15 minutes. Dioxane (8 mL) is added and the reaction mixtureis degassed with argon and stirred at 20-25 degrees C. overnight. Thereaction mixture is diluted with ether, washed with saline, dried overmagnesium sulfate and concentrated under reduced pressure to give methyl3-[(dipropylamino)carbonyl]-5-(3-thienyl)benzoate (XLIX) which ispurified by flash chromatography (silica; ethyl acetate/hexanes, 1/1),ESI-MS (m/z) [M+H]⁺=346.

[1803] Step 4:

[1804] A mixture of methyl3-[(dipropylamino)carbonyl]-5-(3-thienyl)benzoate (XLIX, step 3, 0.31 g,0.88 mmol) in THF/methanol/sodium hydroxide (3/1/1, 5 mL) is stirred at40 degrees C. for 2 hours. The reaction is cooled to 20-25 degrees C.,diluted with water and extracted with ethyl acetate. The aqueous phaseis acidified to pH=4 and extracted with ethyl acetate. The organic phaseis washed with water and saline, dried over magnesium sulfate andconcentrated under reduced pressure to give3-[(dipropylamino)carbonyl]-5-(3-thienyl)benzoic acid (IX-L), ESI-MS(m/z) [M+H]⁺=332.

[1805] Step 5:

[1806] A mixture of 3-[(dipropylamino)carbonyl]-5-(3-thienyl)benzoicacid (IX-L, step 4, 0.26 g, 0.79 mmol),(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII, 0.26 g, 0.71 mmol), HOBt (0.16 g, 1.18 mmol), andtriethylamine (0.44 mL, 3.15 mmol) in DMF (4 mL) is stirred at 20-25degrees C. for 10 minutes EDC (0.23 g, 1.18 mmol) is added and thereaction mixture is stirred for 4 hours. The reaction mixture is dilutedwith water and extracted with ethyl acetate. The organic phase is washedwith hydrochloric acid (1 N), water, and saline, dried over magnesiumsulfate and concentrated under reduced pressure. Recrystallization(methylene chloride/hexanes, 1/1) gives the title compound, mp=199-201degrees C.; IR (KBr): 3278, 2961, 2874 and 2837 cm⁻¹; ESI-MS (m/z)[M+H]⁺=614.

Example 753N-{(1R,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide(X)

[1807] Step 1:

[1808] To an ice-cold, stirred mixture of oxalyl chloride (733 mg, 5.77mmol) in methylene chlorOide (5 mL) is added 3 drops ofdimethylformamide. After 10 minutes 3-(methoxycarbonyl)-5-methylbenzoicacid (LXXIII, 560 mg, 2.89 mmol) is added. The reaction mixture isstirred for 1 hour and concentrated under reduced pressure to provide anacid chloride (LXXIV), which is used without further purification.

[1809] Step 2:

[1810] To a −78 degrees C., stirred mixture of acid halide (LXXIV, step1, 612 mg, 2.89 mmol) and copper (I) bromide (415 mg, 2.89 mmol) intetrahydrofuran (5 mL) is added butyl magnesium chloride (1.44 mL of a2.0 M mixture in tetrahydrofuran, 2.89 mmol). The reaction mixture iswarmed to 20-25 degrees C., quenched by addition of saturated ammoniumchloride, and diluted with ether. The organic phase is separated, washedwith saline, dried (sodium sulfate), filtered, and concentrated underreduced pressure. Purification by flash column chromatography (silica;hexanes/ethyl acetate, 6.5/1) gives methyl 3-methyl-5-pentanoylbenzoate(LXXVI), NMR (300 MHz, CD₃OD): δ 8.43, 8.05, 3.96, 3.01, 1.77, 1.55 and1.22.

[1811] Step 3:

[1812] A mixture of methyl 3-methyl-5-pentanoylbenzoate (LXXVI, step 2.133 mg, 0.605 mmol) in methanol (1 mL) is stirred withtetrahydrofuran/methanol/sodium hydroxide (2 N) (3/1/1, 3 mL) for 3days. The reaction mixture is diluted with ethyl acetate and washed withwater. The aqueous phase is separated and acidified with hydrochloricacid (1 N) and extracted with methylene chloride. The organic phase isdried (sodium sulfate), filtered, and concentrated under reducedpressure to give 3-methyl-5-pentanoylbenzoic acid (IX-LXXVII), NMR (300MHz, CD₃OD): δ 8.44, 8.03, 3.10, 2.33, 1.78, 1.64 and 1.34.

[1813] Step 4:

[1814] To a mixture of 3-methyl-5-pentanoylbenzoic acid (IX-LXXVII, 112mg, 0.589 mmol),(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanoldihydrochloride (VIII, 239 mg, 0.589 mmol), HOBt (80 mg, 0.589 mmol),and N-methylmorpholine (250 mg, 2.47 mmol) in methylene chloride (3 mL)is added EDC (203 mg, 1.06 mmol). The reaction mixture is stirredovernight and then partitioned between ethyl acetate and water. Theorganic phase is washed with hydrochloric acid (1 N), saturated sodiumbicarbonate, saline, dried (sodium sulfate), filtered, and concentratedunder reduced pressure. Purification by flash column chromatography(silica; methylene chloride/methanol, 12/1) gives the title compound, IR(ATR): 3297,2957, 1687 and 1628 cm⁻¹; APCI-MS (m/z) [M+H]⁺=539.

Example 754N¹-(4-hydroxybutyl)-N³-{(1S)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N¹-propylisophthalamide(X)

[1815] Step 1:

[1816] To a mixture of methyl(2S)-3-[4-(benzyloxy)phenyl]-2-(tert-butoxycarbonyl)aminopropanoate(1.79 g, 4.65 mmol) in a TIF/methanol/water (1/2/1, 16 ml) is addedlithium hydroxide (340 mg, 13.9 mmol) and the mixture stirred at 20-25degrees C. for 12 hours. The mixture is quenched with citric acid (10%).The resulting mixture is extracted with ethyl acetate (3×15 ml). Thecombined organic extracts are washed three times with water, dried oversodium sulfate, filtered, and concentrated under reduced pressure togive(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propanoicacid which is carried on without purification. To a −78 degrees C.,stirred mixture of(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propanoicacid (10.0 g, 27.0 mmol) in THF (200 mL) is added NMM (3.20 mL, 29.0mmol) and isobutyl chloroformate (3.8 mL, 29.0 mmol). The cold bath isremoved, the reaction mixture is stirred for 1 hour, and then filtered.The filtrate is kept cold and used in the next step. To an ice-cold,stirred mixture of ether (110 mL) and potassium hydroxide (40%, 35 mL)is slowly added 1-methyl-3-nitro-1-nitrosoguanidine (8.40 g, 57.0 mmol).The reaction mixture is stirred until gas evolution ends. The organicphase is separated and slowly added to an ice-cold, stirred mixture ofthe mixed anhydride filtrate from step 2. After the reaction mixture isstirred for 1 hour, nitrogen is bubbled into the mixture for 10 minutesThe resulting mixture is concentrated under reduced pressure, dilutedwith ethyl acetate (200 mL), and washed with water (100 mL). The organicphase is washed with saturated sodium bicarbonate and saline, dried oversodium sulfate, filtered, and concentrated under reduced pressure togive the diazoketone, which is carried on without purification orcharacterization. To an ice-cold, stirred mixture of diazoketone inether (100 mL) is added hydrobromous acid (48%, 4 mL, 73 mmol). The coldbath is removed, the reaction mixture stirred for 30 minutes, andpartitioned between ether and water. The organic phase separated andwashed with saturated sodium bicarbonate and saline, dried over sodiumsulfate, filtered, and concentrated under reduced pressure to givetert-butyl (1S)-1-[4-(benzyloxy)benzyl]-3-bromo-2-oxopropylcarbamate(IV) which is used without further purification or characterization. Toa −78 degrees C., stirred mixture of tert-butyl(1S)-1-[4-(benzyloxy)benzyl]-3-bromo-2-oxopropylcarbamate (IV) in aisopropanol/THF (2/1, 150 mL) is slowly added sodium borohydride (1.15g, 30.0 mmol). The reaction mixture is stirred for 30 minutes followedby the addition of water (30 mL). The resulting mixture is warmed to20-25 degrees C. and concentrated under reduced pressure in a water bathnot exceeding 30 degrees C. The crude residue is dissolved in ethylacetate and washed with water and saline. The organic phase is driedover magnesium sulfate, filtered and concentrated under reduced pressureto give the bromohydrin as a solid. To an ice-cold, stirred mixture ofbromohydrin in ethanol (150 mL) and ethyl acetate (100 ml) is added apotassium hydroxyde (1 N) ethanol mixture (36 mL, 36 mmol). The coldbath is removed and the reaction mixture is stirred for 30 minutes. Theresulting mixture is partitioned between ethyl acetate and water. Theorganic phase is separated and washed with saline, dried over magnesiumsulfate, filtered, and concentrated under reduced pressure. Purificationby flash chromatography (silica; hexanes/ethyl acetate, 511) givestert-butyl (1S)-2-[4-(benzyloxy)phenyl]-1-[(2S)-oxiranyl]ethylcarbamate(V, as a 8/1 mixture of diastereomers), NMR (500 MHz, CDCl₃) δ7.44-7.32, 7.14, 6.93, 5.07, 4.45, 3.61, 3.00-2.60 and 1.39.

[1817] Step 2:

[1818] A mixture of 4-benzyloxybutyric acid (2.69 g, 13.8 mmol),propylamine (0.82 g, 13.8 mmol), HOBt (2.05 g, 15.2 mmol),N-methylmorpholine (1.68 g, 16.6 mmol) and EDC (2.91 g, 15.2 mmol) inDMF (6 mL) is stirred at 20-25 degrees C. for 18 hours. The mixture isdiluted with ethyl acetate (40 mL) and washed with water (10 mL),hydrochloric acid (1 N, 10 mL), saturated sodium bicarbonate (10 mL),and saline (10 mL). The organic phase is separated, dried over magnesiumsulfate, filtered, and concentrated under reduced pressure to provide4-(benzyloxy)-N-propylbutanamide (2.59 g), APCI-MS (m/z) [M+H]⁺=236.

[1819] Step 3:

[1820] To an ice-cold, stirred mixture of4-(benzyloxy)-N-propylbutanamide (2.59 g, 11.0 mmol) in THF (8 mL) isadded lithium aluminum hydride (0.54 g, 14.3 mmol). The reaction mixtureis heated to 40-50 degrees C. for 5 hours. The cooled reaction mixtureis quenched with water (0.5 irL), sodium hydroxide (2 N, 1.0 mL), andsaline (0.5 mL) then diluted with ether (30 mL). The precipitate thatformed is filtered off, and the ether phase dried over magnesiumsulfate, filtered, and concentrated under reduced pressure to giveN-[4-(benzyloxy)butyl]-N-propylamine (2.41 g), APCI-MS (m/z): 222[M+H]⁺.

[1821] Step 4:

[1822] A mixture of N-[4-(benzyloxy)butyl]-N-propylamine (2.31 g, 10.44mmol), 3-(ethoxycarbonyl)-5-methylbenzoic acid (2.18 g, 10.44 mmol),HOBt (1.56 g, 11.49 mmol), N-methylmorpholine (1.37 mL, 12.52 mmol), andEDC (2.20 g, 11.49 mmol) in DMF (12 mL) is stirred at 20-25 degrees C.for 18 hours. The reaction mixture is diluted with ethyl acetate (80 mL)and washed with water (2×20 mL), hydrochloric acid (1 N, 20 mL),saturated sodium bicarbonate (20 mL) and saline (20 mL), dried overmagnesium sulfate, filtered, and concentrated under reduced pressure.Purification by flash chromatography (silica; hexanes/ethyl acetate,1/1)gives ethyl3-{[[4-(benzyloxy)butyl](propyl)amino]carbonyl}-5-methylbenzoate (1.79g), NMR (500 MHz, DMSO-d₆): delta7.80, 7.64, 7.40, 7.38-7.16, 4.50-4.43,4.34-4.29, 3.53-3.30, 3.20-3.06, 2.41-2.36, 1.70-1.40, 1.36-1.29,0.94-0.84 and 0.82-0.72; APCI-MS (m/z) [M+H]⁺=412.

[1823] Step 5:

[1824] To a mixture of ethyl3-{[[4-(benzyloxy)butyl](propyl)-amino]carbonyl}-5-methylbenzoate (1.75g, 4.25 mmol) in THF/ethanol/water (1/2/1, 30 mL) is added lithiumhydroxide (0.31 g, 12.76 mmol). The reaction mixture is stirred for 2 hand then acidified to pH=3 with concentrated hydrochloric acid (0.5 mL).The reaction mixture is extracted with ethyl acetate (2×30 mL), driedover magnesium sulfate, filtered, and concentrated under reducedpressure to give3-{[[4-(benzyloxy)butyl](propyl)amino]carbonyl}-5-methylbenzoic acid(IX, 1.63 g), ESI-MS (m/z) [M +H]⁺=384.

[1825] Step 6:

[1826] A mixture of tert-butyl(1S)-2-[4-(benzyloxy)phenyl]-1-[(2S)-oxiranyl]ethylcarbamate (V, 1.58 g,4.28 mmol) and 3-methoxybenzylamine (VI, 825 microliter, 6.42 mmol) inisopropanol (45 mL) is heated to 90 degrees C. for 4 hours. Upon coolingto 20-25 degrees C., the reaction mixture is concentrated under reducedpressure. Purification by flash chromatography (silica; methylenechloride/methanol/ammonium hydroxide 98/1/1 to 95/:4/1) gives tert-butyl(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII, 1.97 g), NMR (300 MHz, MeOH-d₄): δ 7.41-6.79, 5.05, 4.33-3.33,3.74, 3.54, 3.03-2.46 and 1.29; ESI-MS (m/z) [M+H]⁺=507.

[1827] Step 7:

[1828] tert-Butyl(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate(VII, step 6, 2.34 g, 4.62 mmol) in dioxane (10 mL) is treated withhydrochloric acid (12 mL of a 4.0 M mixture in dioxane, 48 mmol) for 2hours. The precipitate that forms is collected by filtration, washedwith ether, and dried under reduced pressure overnight to give(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-1-[(3-methoxybenzyl)amino]-2-butanolhydrochloride (VIII), NMR (300 MHz, MeOH-d₄): δ 7.44-6.96, 5.05, 4.21,3.83, 3.65) and 3.21-2.77; ESI-MS (m/z) [M+H]⁺=407.

[1829] Step 8:

[1830] To an ice-cold, stirred mixture of3-{[[4-(benzyloxy)butyl](propyl)amino]carbonyl}-5-methylbenzoic acid(IX, 310 mg, 0.809 mmol),(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-1-[(3-methoxybenzyl)amino]-2-butanolhydrochloride (VIII, 359 mg, 0.809 mmol), andbromotripyrrolidinophosphonium hexafluorophosphate (415 mg, 0.890 mmol)in methylene chloride (10 mL) is added diisopropylethylamine (285microL, 1.62 mmol) dropwise. The resulting mixture is stirred at 0degrees C. for 30 minutes and then warmed to 20-25 degrees C. After 4hours, the reaction is concentrated under reduced pressure and ispartitioned between ethyl acetate and water. The aqueous phase isseparated and extracted with ethyl acetate (3×15 mL), the combinedorganic phases are dried over magnesium sulfate, and concentrated underreduced pressure. The concentrate is purified by flash chromatography(silica; methylene chloride/methanol/ammonium hydroxide 96/3/0.5) togiveN¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-[4-(benzyloxy)butyl]-5-methyl-N³-propylisophthalamide(X) NMR (300 MHz, Acetone-d₆): delta 7.99-6.74), 5.01 4.51-4.29, 4.36,4.01, 3.80, 3.55-3.16, 2.98-2.82, 2.65-2.62, 2.36, 1.85-1.29, 1.01 and0.68; ESI-MS (m/z) [M +H]⁺=772.

[1831] Step 9.

[1832] A mixture ofN¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-[4-(benzyloxy)butyl]-5-methyl-N³-propylisophthalamide(X, 100 mg, 0.130 mmol) and palladium on carbon (10%, 100 mg) inabsolute glacial acetic acid (5 mL) is shaken under an atmosphere ofhydrogen at 35 psi for 5 hours. The resulting mixture is filteredthrough diatomaceous earth and washed with methanol. The combinedfiltrates are concentrated under reduced pressure. The concentrate ispurified by flash column chromatography (silica; gradent ofdichloromethane/methanol/ammonium hydroxide 97/3/0.05 to 93/7/0.05) togive the title compound: NMR (300 MHz, CD₃OD): δ 7.55-6.64, 4.19,3.99-3.72, 3.63-3.36, 3.21-3.09, 2.79-2.69, 2.39, 1.90-1.40, 1.29 and1.02-0.6; ESI-MS (m/z) [M +H]⁺=592.

Example 755N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³-(3-hydroxypropyl)-5-methyl-N³-propylisophthalamide(X)

[1833] Following the general procedure of EXAMPLE 754 and makingnon-critical variations, but using3-{[[3-(benzyloxy)propyl](propyl)amino]carbonyl}-5-methylbenzoic acid(IX) in place of3-{[[4-(benzyloxy)butyl](propyl)amino]-carbonyl}-5-methylbenzoic acid(IX), the title compound is obtained, ESI-MS (m/z) [M+H]⁺=578.

Example 756N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1834] Step 1.

[1835] To a stirred mixture of3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (IX, 150 mg, 0.570mmol),(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-1-[(3-methoxybenzyl)amino]-2-butanolhydrochloride (VIII, 274 mg, 0.571 mmol), N,N-diisopropylethylamine (400microliter, 2.28 mmol), and HOBt (116 mg, 0.857 mmol) in dichloromethane(10 mL) is added EDC (165 mg, 0.857 mmol). The resulting mixture isstirred at 20-25 degrees C. for 16 hours. The reaction mixture ispartitioned between dichloromethane and water. The aqueous phase isseparated and extracted with dichloromethane (3×15 mL). The combinedorganic phases are washed with water, dried (magnesium sulfate), andconcentrated under reduced pressure.

[1836] Purification by flash column chromatography (silica;dichloromethane/methanol/ammonium hydroxide, 97/3/0.05) givesN¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide,ESI-MS (m/z) [M +H]⁺=652.

[1837] Step 2.

[1838] A mixture ofN-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(140 mg, 0.215 mmol) and palladium on carbon (10%, 140 mg) in absoluteglacial acetic acid (5 mL) is shaken under an atmosphere of hydrogen at35 psi for 5 hours The resulting mixture is filtered throughdiatomaceous earth and washed with methanol. The 10 combined filtratesare concentrated under reduced pressure. The concentrate is purified byflash column chromatography (silica; methylenechloride/methanol/ammonium hydroxide gradient from 97/3/0.05 to93/7/0.05) to give the title compound, IR (KBr) 2962, 2931, 1611, 1594and 1263 cm⁻¹; ESI-MS (m/z) [M+H]⁺=562.

[1839] EXAMPLE 757

N¹-((1S,2R)-1-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide(X)

[1840] Step 1:

[1841] A stirred mixture of tert-butyl (1S)-1-[(2S)-oxiranyl]-2-20phenylethylcarbamate (V, 247 mg, 0.939 mmol), sodium carbonate (299 mg,2.82 mmol), and 3-(2,4-dimethylphenyl)propylamine (VI, 628 mg, 2.82mmol) is heated at reflux overnight. The reaction mixture is cooled to20-25 degrees C. and concentrated under reduced pressure. Purificationby flash column chromatography (silica; methylenechloride/methanol/ammonium hydroxide, 98/2/1) gives tert-butyl(1S,2R)-251-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropylcarbamate(VII), NMR (300 MHz, CD₃OD): delta 7.22-7.16, 3.81, 3.18, 2.77, 2.54,2.15, 2.13, 1.89 and 1.23.

[1842] Step 2:

[1843] To a stirred mixture of tert-butyl(1S,2R)-1-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropylcarbamate(VII, 180 mg, 0.423 30 mmol) in dioxane (2 mL) is added hydrochloricacid (0.32 mL of a 4 N mixture in dioxane, 1.27 mmol). The reactionmixture is stirred overnight and concentrated under reduced pressure togive(2R,3S)-3-amino-1-{[3-(2,4-dimethylphenyl)propyl]amino}-4-phenyl-2-butanolhydrochloride (VIII), NMR (300 MHz, CDCl₃): delta 7.14, 3.73, 2.70, 2.32and 1.86.

[1844] Step 3:

[1845] To a stirred mixture of(2R,3S)-3-amino-1-{[3-(2,4-dimethylphenyl)propyl]amino}-4-phenyl-2-butanolhydrochloride (VIII, 163 mg, 0.411 mmol),3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (IX, 108 mg, 0.411mmol), HOBt (55 mg, 0.411 mmol), and N-methylmorpholine (133 mg, 1.32mmol) in methylene chloride (5 mL) is added EDC (142 mg, 0.740 mmol).The reaction mixture is stirred overnight and then partitioned betweenethyl acetate and water. The organic phase is washed with hydrochloricacid (1 N), saturated sodium bicarbonate, saline, dried (sodiumsulfate), filtered, and concentrated under reduced pressure.Purification by flash column chromatography (silica; methylenechloride/methanol/ammonium hydroxide, 95/5/1) gives the title compound,IR (ATR): 3299, 2930 and 1614 cm⁻¹; APCI-MS (m/z) [M +H]⁺=572.

Example 758N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-methylphenyl)propyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamidehydrochloride (X)

[1846] Following the general procedure of EXAMPLE 757 and makingnon-critical variations, but using 3-(4-methylphenyl)propylamine inplace of 3-(2,4-dimethylphenyl)propylamine, the title compound isobtained, IR (ATR): 3282, 2929 and 1594 cm⁻¹; APCI-MS (m/z) [M +H]⁺=558.

Example 759N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1847] Following the general procedure of EXAMPLEs 4, 5, and 6 andmaking non-critical variations but using tert-butyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and “5-Me-PHTH” (IX), the title compound isobtained, MS [M+H]⁺=546.3.

Example 760N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1,3-dioxo-2-propyl-5-isoindolinecarboxamide(X)

[1848] Following the general procedure of EXAMPLEs 4, 5, and 6 andmaking non-critical variations but using tert-butyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and 1,3-dioxo-2-propylisoindoline-5-carboxylicacid (IX), the title compound is obtained, MS [M+H]⁺=516.2.

Example 761N-{(1R,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-bromo-5-methylbenzamide(X)

[1849] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using benzyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-bromo-5-methylbenzoic acid (IX), thetitle compound is obtained, MS [M+H]⁺=497.1, 499.1.

Example 7623-bromo-N-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide(X)

[1850] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-cntical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-bromo-5-methylbenzoic acid (IX), thetitle compound is obtained, MS [M+H]⁺=533.3, 535.3.

Example 763N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide(X)

[1851] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using benzyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-[(dipropylamino)carbonyl]4-methylbenzoicacid (IX), the title compound is obtained, MS [M+H]⁺=546.4.

Example 764N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide(X)

[1852] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-[(dipropylamino)carbonyl]4-methylbenzoicacid (IX), the title compound is obtained, MS [M+H]⁺=582.3.

Example 765N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N¹,N¹-dipropylisophthalamide(X)

[1853] 3-Bromo-4-methylbenzoic acid (10.94 g, 43.25 mmol),copper(I)cyanide (7.75 g, 86.5 mmol) and 1-methyl-2-pyrrolidinone (75ml) are heated to 160 degrees C. overnight. The mixture is cooled andvacuum distilled to give a residue which is stirred in hydrochloric acid(6N, 60 ml) for 10 minutes. The resulting solid is collected byfiltration, washed with water, ether, and dried. The solid is heated to90 degrees C. in sodium hydroxide (2N, 250 ml) for 3 hours and themixture is then cooled and stirred overnight at 20-25 degrees C. Thereaction is acidified to about pH 3 with concentrated hydrochloric acidwhich gives a precipitate. The solids are collected by filtration andwashed with water, then triturated in boiling water, filtered and driedin a vacuum oven at 60 degrees C. The solid is dissolved in methanol (75ml) and concentrated hydrochloric acid (5 ml) is added and the mixtureis refluxed overnight. The mixture then is cooled and concentrated underreduced pressure. Chromatography (silica gel; methanol/methylenechloride, 8/92) gives 5-(methoxycarbonyl)-2-methylbenzoic acid.

[1854] To 5-(methoxycarbonyl)-2-methylbenzoic acid (250 mg, 1.3 mmol)and triethylamine (0.72 ml, 5.2 mmol) in methylene chloride (14 ml) isadded diethylcyanopyrocarbonate (90%, 0.24 ml, 1.4 mmol) with stirring.After 1 minute,(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanoldihydrochloride (VIII, 485 mg, 1.3 mmol) is added and the reaction isstirred overnight. The mixture is concentrated followed bychromatography (silica gel; methanol/methylene chloride 8/92) to afford3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-4-methylbenzoate.

[1855]3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]4-methylbenzoate (200 mg, 0.42 mmol) is treated with lithiumhydroxide (39 mg, 0.96 mmol) in tetrahydrofuran/methanol/water (2/1/1, 2ml), and the mixture stirred overnight at 20-25 degrees C. The mixtureis decanted and the supernatant concentrated to give3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-4-methylbenzoicacid.

[1856]3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-4-methylbenzoic acid (124 mg, 0.27 mmol) is dissolved intriethylamine (0.07 ml, 0.54 mmol) and methylene chloride (3 ml) andtreated with diethylcyanopyrocarbonate (90%, 0.06 ml, 0.32 mmol) withstirring for 2 minutes. Dipropylamine (0.04 ml, 0.32 mmol) is added andstirring continued overnight. The organic phase is diluted withmethylene chloride and washed with saturated sodium bicarbonate (2×50ml) and saline (50 ml) then dried over anhydrous sodium sulfate,filtered and concentrated. Chromatography (silica gel;methanol/methylene chloride, 8/92) gives the title compound, MS[M+H]⁺=546.3.

Example 766N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(2-furyl)-5-methylbenzamide(X)

[1857]N-{(1R,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-bromo-5-methylbenzamide(X, EXAMLE 761, 295 mg, 0.59 mmol), 2-furanylboronic acid (133 mg, 1.19mmol) and sodium carbonate (366 mg, 2.95 mmol) are combined indimethylformamide (5 ml) and sparged under a flow of nitrogen for 15minutes. Tetrakis(triphenylphosphino)palladium (136 mg, 0.12 mmol) isadded and the mixture heated to 100 degrees C. overnight. The mixture iscooled to 20-25 degrees C., diluted with chloroform (50 ml) andextracted with water (3×100 ml). The organic phase is separated andwashed with saturated sodium bicarbonate (2×100 ml) and saline (100 ml),dried over anhydrous sodium sulfate, filtered, and concentrated underreduced pressue. The residue is chouromatographed (silica gel;methanol/methylene chloride, 8/92) to give the title compound, MS[M+H]⁺=485.3.

Example 767N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3′,5,5′-trimethyl-1,1′-biphenyl-3-carboxamide(X)

[1858] Following the general procedure of EXAMPLE 766 and makingnon-critical variations but using 3,5-dimethylphenylboronic acid, thetitle compound is obtained, MS [M+H]⁺=523.3.

Example 7683′-Acetyl-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl[1,1′-biphenyl]-3-carboxamide(X)

[1859] Following the general procedure of EXAMPLE 766 and makingnon-critical variations but using 3-acetylphenylboronic acid, the titlecompound is obtained, MS [M+H]⁺=537.3.

Example 769N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3′-methoxy-5-methyl[1,1′-biphenyl]-3-carboxamide(X)

[1860] Following the general procedure of EXAMPLE 766 and makingnon-critical variations but using 3-methoxyphenylboronic acid, the titlecompound is obtained, MS [M+H]⁺=525.3.

Example 770N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl[1,1′-biphenyl]-3-carboxamide(X)

[1861] Following the general procedure of EXAMPLE 766 and makingnon-critical variations but using phenylboronic acid, the title compoundis obtained, MS [M+H]⁺=495.3.

Example 771 3-Methyl-5-(3-thienyl)benzoic acid (IX)

[1862] Following the general procedure of EXAMPLE 766 and makingnon-critical variations but using 2-thiopheneboronic acid and methyl3-bromo-5-methylbenzoate, methyl 3-methyl-5-(3-thienyl)benzoate isobtained.

[1863] Methyl 3-methyl-5-(3-thienyl)benzoate (257 mg, 1.1 mmol) istreated with lithium hydroxide (186 mg, 4.4 mmol) intetrahydrofuran/methanol/water (8 ml, 2:1:1) and the mixture is stirredfor 2 hours at 20-25 degrees C. The mixture is acidified andconcentrated to give the title compound, MS [M+H]⁺=217.0.

Example 772N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(3-thienyl)benzamide(X)

[1864] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using benzyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-methyl-5-(3-thienyl)benzoic acid (IX),the title compound is obtained, MS [M+H]⁺=501.2.

Example 773N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(2-thienyl)benzamide(X)

[1865] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using benzyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-methyl-5-(2-thienyl)benzoic acid, thetitle compound is obtained, MS [M+H]⁺=501.2.

Example 774N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(3-thienyl)benzamide (X)

[1866] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-methyl-5-(3-thienyl)benzoic acid (IX),the title compound is obtained, MS [M+H]⁺=537.2.

Example 775N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methyl-5-(3-thienyl)benzamide(X)

[1867] Following the general procedure of EXAMPLEs 4, 5 and 6 and makingnon-critical variations but using tert-butyl(1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate (V) and3-iodobenzylamine (VI) and 3-methyl-5-(3-thienyl)benzoic acid (IX), thetitle compound is obtained, MS [M+H]⁺=633.1.

Example 776N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-3-(3-thienyl)benzamide(X)

[1868] Following the general procedure of EXAMPLEs 4, 5, 6 and 766 andmaking non-critical variations but using benzyl(1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V) and3-methoxybenzylamine (VI) and 3-bromo-4-methylbenzoic acid (IX) and3-thiopheneboronic acid, the title compound is obtained, MS[M+H]⁺=501.2.

Example 777N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³N³,N⁵,N⁵-tetrapropylbenzene-1,3,5-tricarboxamidehydrochloride (X)

[1869] Following the general procedures of CHART A as well asPREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, HRMS (FAB)=659.4155.

Example 778N¹-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide(X)

[1870] Following the general procedures of CHART A as well asPREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=609.2.

Example 779 Ethyl3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoatehydrochloride (X)

[1871] Following the general procedures of CHART A as well asPREPARATIONs 1-13, EXAMPLEs 1-13, 32148-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, HRMS (FAB)=604.3392.

Example 780N¹-{(1S,2R)-2-Hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide(X)

[1872] Following the general procedures of CHART A as well asPREPARATIONs 1-13, EXAMPLEs 1-13, 32148-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=591.0.

Example 781N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide(X)

[1873] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=679.2.

Example 7825-Amino-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide(X)

[1874] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=547.3.

Example 783N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(trifluoroacetyl)amino]isophthalamide(X)

[1875] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 32148-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=643.2.

Example 784N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamidehydrochloride (X)

[1876] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 32148-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=625.0.

Example 785N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamidehydrochloride (X)

[1877] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=693.1.

Example 786N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylcarbonyl)amino]isophthalamide(X)

[1878] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=657.2.

Example 787N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methacryloylamino)-N³,N³-dipropylisophthalamide(X)

[1879] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=615.1.

Example 788N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(2,2-dimethylpropanoyl)amino]-N³,N³-dipropylisophthalamide(X)

[1880] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 32148-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=631.3.

Example 789N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalainide(X)

[1881] Following the general procedures of CHART A and CHART T as wellas PREPARATIONs 1-13, EXAMPLEs 1-13, 321-48-579, 597-622 and 624-631 andmaking non-critical variations and using the appropriate reagents, thetitle compound is obtained, MS (M+H)⁺=687.2.

Example 790N-{(I1S,2R)-l1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methylthio)pentanamide

[1882] Following the general procedure of EXAMPLEs 588-592 and 597-619and using the appropriate starting materials the title compound isobtained, HRMS m/z calculated for C₂₄H₃₅N₂O₃S (M+H)=431.2363, found=431.2397.

Example 791 tert-butyl(2R,3S)-3-({3-[(dipropylamino)sulfonyl]-propanoyl}amino)-2-hydroxy-4-phenylbutyl(3-methoxybenzyl)carbamate

[1883] Following the general procedure of EXAMPLEs 588-592 and 597-619and using the appropriate starting materials the title compound isobtained, HRMS calculated for M+H is 620.3369, observed=620.3379.

Example 792 2-Butylcyclopropylamine hydrochloride (VI)

[1884] A solution of triethylphosphonoacetate (22.4 g, 0.1I mol) in 13mL of diglyme is added to a mixture of 13 mL of diglyme and sodiumhydride (60%, 5.7 g, 0. 12 mol) in mineral oil. When hydrogen evolutionceased, 1,2-epoxyhexane (12 g, 0.12 mol) in diglyme (12 mL) is added.The mixture is stirred for I day at 25 degrees C. and 3 hours at 140degrees C. A mixture of sodium hydroxide (15 g in 25 mL of water) isadded in the cold. The mixture is refluxed 15 hours, diluted with coldwater (100 mL), and washed with ether (3×50 mL). Acidification to pH=2with sulfuiric acid (25%), extraction with ether (5×25 mL), drying theether over anhydrous sodium sulfate, filtration and concentration gives2-butylcyclopropanecarboxylic acid. The acid (5.0 g, 0.035 mmol) indichloromethane (15 mL) is heated with thionyl chloride (5.1 g, 3.1 mL)for 15 hours at 60 degrees C. The reaction mixture is distilled (76degrees C.-80 degrees C.) to give the acid chloride which is dissolvedin acetone (15 mL), cooled to −10 degrees C. and treated with sodiumazide (2.2 g, 33.8 mmol) in water (5 mL). The reaction mixture isstirred at −10 degrees C. for another 1 hour and then poured ontoice/water, extracted with ether (3×10 mL), dried, and cautiouslyevaporated to dryness at 20-25 degrees C. under reduced pressure. Theresidue is dissolved in toluene (15 mL) and carefully warmed to 100degrees C. while vigorously stirring for 1 hour. Concentratedhydrochloric acid (7 mL) is added and the reaction mixture is refluxedfor 15 minutes. The acidic layer is evaporated to dryness to give thetitle compound, MH⁺=114.2.

Example 793 2-Aminomethyl-3-methylfuran (VI)

[1885] 3-Methylfuroic acid (4.0 g, 32 mmol) is dissolved in DMF (10 mL)at 20-25 degrees C., and 1,1-carbonyldiimidazole (5.7 g, 35 mmol) isadded. After 15 minutes, ammonia is bubbled into the mixture forapproximately 2 minutes. This mixture is stirred at 20-25 degrees C. for2 hours then the mixture is concentrated under reduced pressure. Theresidue is partitioned between ethyl acetate and 10% aqueous citricacid. The layers are separated, and the aqueous layer extracted withadditional ethyl acetate (2×). The combined organic phases are washedwith saturated sodium bicarbonate, then saline and dried over magnesiumsulfate, filtered and concentrated. Crystals formed upon standing, whichare isolated by filtration and washing with a small amount of ethylacetate/hexanes (80/20), MS(ESI): MH+: 126.1. 3-Methylfuroic amide (317mg, 2.5 mmol) is dissolved in dry THF (5 mL). Lithium aluminum hydride(230 mg, 6.0 mmol) is added in one portion, and the mixture heated toreflux overnight. The mixture is cooled to 0 degrees C., and quenched byaddition of THF/water (50/50). The mixture is then diluted with THF, andfiltered through diatomaceous earth. The filtrate is concentrated togive the title compound, MS(ESI): (M−H)+: 109.1.

Example 794 4-Aminomethyl-3,5-dimethylisoxazole (VI)

[1886] 4-Chloromethyl-3,5-dimethylisoxazole (700 mg, 4.8 mmol) issuspended in concentrated aqueous ammonia at 20-25 degrees C., andvigorously stirred overnight. The reaction mixture is extracted withisopropyl alcohol/chloroform (10/90, 2×). The combined organic phasesare concentrated under nitrogen flow. The residue is purified by flashchromatography methanol/methylene chloride (5-20%, 1% triethylamine) togive the title compound, MR (CDCl₃, 300 MHz) delta3.62, 2.37, 2.29, and1.44.

Example 795 5-Hydroxymethyl-2-(2-methylpropyl) thiazole (VI)

[1887] Isovalerothioamide is synthesized according to the procedure inJ. Med. Chem. 41, 602-617 (1998). Isovaleramide (10 g, 9.9 mmol) issuspended in dry ether (400 mL), then phosphorous(V) sulfide (4.4 g,0.99 mmol) is added in portions. This is vigorously stirred at 20-25degrees C. for 2 hours, then filtered. The filtrate is concentratedunder reduced pessure and the residue used without further purification:MS(ESI): MH+: 118.1.

[1888] Isovalerothioamide (6.0 g, 51 mmol) and ethyl formylchloroacetate(Heterocycles 32 (4), 693-701, (1991), 5.0 g, 33 mmol) are dissolved indry DMF (20 mL), and heated to 95 degrees C. for 4 hours. The reactionis subsequently cooled to 0 degrees C., and cold water (50 mL) is added.The mixture is basified to pH=8 with solid sodium bicarbonate, thenextracted with ether (3×35 mL). The combined organic extracts are washedwith water, then saline and dried over magnesium sulfate, filtered, andconcentrated. The residue is purified by flash chromatography (ethylacetate/hexanes 4-10% elution) to give the desired product. NMR (CDCl₃,300 MHz) δ 8.27, 4.45-4.30, 3.70-3.50, 3.00-2.80, 2.30-2.10, 1.40-1.20,and 1.10-0.90.

[1889] A solution of ethyl 2-(2-methylpropyl)thiazole-5-carboxylate(2.05 g, 9.6 mmol) in THF (10 mL) is added dropwise with stirring to asuspension of lithium aluminum hydride (730 mg, 19 mmol) in dry THF (50mL) at 0 degrees C. Upon complete addition, the reaction mixture isallowed to stir at 20-25 degrees C. The reaction mixture is cooled to 0degrees C., and water (0.75 mL), aqueous sodium hydroxide (15%, 0.75mL), and water (2.25 mL) is added in succession. This mixture is stirredat 0 degrees C. for 1 hour, then filtered through diatomaceous earth,(THF and chloroform). The filtrate is concentrated to give5-hydroxymethyl-2-(2-methylpropyl)thiazole, MS(ESI): MH+: 172.1.

Example 796 3-(2-Methylpropyl)-5-aminomethylisoxazole (VI)

[1890] Isovaleraldehyde (5.4 mL, 50 mmol) and hydroxylaminehydrochloride (3.5 g, 50.4 mmol) are vigorously stirred in water (6 mL).To this is added a solution of sodium carbonate (2.65 g, 25 mmol) inwater (15 mL). This is vigorously stirred overnight. The mixture isextracted with ether. The organic layer is washed with water, then driedover sodium sulfate, filtered and concentrated. This is used insubsequent reactions without further purification: MS(ESI): MH+: 102.1.

[1891] Propargylamine (8.0 mL, 117 mmol) is dissolved in methylenechloride (60 mL), and di-tert-butyl dicarbonate (25 g, 114 mmol) isadded. This is stirred overnight, and concentrated to provide theBOC-protected propargylamine, which is used without furtherpurification: MS(ESI): MNa+: 178.0.

[1892] BOC-propargylamine (6.2 g, 39.7 mmol) and isovaleroxime (3.97 g,39.3 mmol) is dissolved in methylene chloride (60 mL), and triethylamine(0.55 mL, 3.95 mmol) is added. This is cooled to 0 degrees C., andbleach (5% aqueous solution, 59.1 g) is added dropwise with vigorousstirring. After addition is complete, the mixture is allowed to warm to20-25 degrees C. over 22 hours. The layers are separated, and theaqueous layer is extracted with methylene chloride (2×). The combinedorganic extracts are washed with saline, dried over magnesium sulfate,filtered and concentrated. The residue is purified by chromatography(silica gel, ethyl acetate/hexanes 5-10%) to give the BOC-protectedtitle compound, MS(ESI): MH+: 255.3.

[1893] BOC-protected 3-(2-methylpropyl)-5-aminomethylisoxazole (2.4 g,9.3 mmol) is dissolved in methylene chloride (10 mL) and treated withtrifluoroacetic acid (10 mL) at 20-25 degrees C. This is stirred at20-25 degrees C. for 70 minutes, then concentrated. The product isdissolved in methylene chloride, and washed with aqueous potassiumcarbonate (1 M) until basic (pH=11). The organic layer is isolated,dried over sodium sulfate, filtered and concentrated to give the titlecompound: MS(ESI): MH+: 155.2.

Example 797 tert-butyl (3R)-2-oxo-1-propylazepanylcarbamate (VI)

[1894] To N-t-Boc-D-Lys-OH (10 g, 41.4 mmole) in DMF (4 liters) is addedbenzotriazol-lyloxytripyrrolidino-phosphonium hexafluorophosphate (BOP,18.3 g, 41.4 mmole) and sodium bicarbonate (17.4 g, 206.8 mmole); thereaction is stirred at 20-25 degrees C. for 12 hours. The reaction isthen concentrated to 50 ml volume and diluted with ethyl acetate andwashed with sodium bicarbonate 3×, water, 1M potassium bisulfate andbrine, dried and concentrated. Purification by chromatography on silicagel afforded 5.05 g of the tert-butyl (3R)-2-oxoazepanylcarbamate as asolid; the procedure employed is similar to that described inJ.Med.Chem. 1999, 4193. M+H-(t-Boc) (m/e=129.2), M+Na (m/e=251.1).

[1895] To the above lactam (2 g, 8.77 mmole) in dry THF (20 ml) is addedn-butyllithium /hexane (2.5 M, 5.3 ml, 13.2 mmole) at −78 degrees C.,the reaction is stirred for 1 hour and 1-bromopropane (3.2 ml, 35.1mmole) is added. The reaction is stirred for 1 hour and the cold bathremoved and stirring continued for another 16 hours. Tetrabutylammoniumiodide (0.49 g, 2.63 mmole) is added and the reaction stirred foranother 16 hours. The reaction is partitioned between ethylacetate/hydrochloric acid +ice +water, the mixture is washed with waterand saline and concentrated. Purification by chromatography on silicagel afforded the title compound, MS (M+Na+) 293.3.

Example 798N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide(X)

[1896] Following the procedure described in J Am. Chem. Soc. 1986, 3150,the trifluoroacetic acid salt ofN¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide(92.9 mg, 0.117 mmol) is dissolved in triethylamine (0.2 M, 0.6 mL)before the addition of PdCl₂(PPh₃)₂ (3.3 mg, 0.005 mmol), and copper (I)iodide (1.1 mg, 0.006 mmol). The reaction is heated to reflux. While thereaction is refluxing, trimethylsilylacetylene (0.02 ml, 0.14 nunol) isadded via syringe. The reaction is refluxed for 3 hour under N₂ (g), andthe reaction cooled to 20-25 degrees C. before partitioning betweenaqueous sodium bicarbonate and ethyl acetate. The product is extractedwith ethyl acetate (3×), washed with saline, dried over sodium sulfate₄,and filtered before the removal of solvent under reduced pressure.

[1897] The TMS protected acetylene (0.117 mmol) is dissolved in methanol(0.2 M, 0.5 mL) before the addition of potassium hydroxide (1M, 0.7 mL,0.7 mmol). The reaction is stirred at 20-25 degrees C. for 6 hours, atwhich point the mixture is partitioned between sodium bicarbonate andethyl acetate. The product is extracted with ethyl acetate (3×), washedwith saline, dried over sodium sulfate, and filtered before the removalof solvent under reduced pressure. Column chromatography (silica gel;1.5-2% isopropanol/chloroform under basic conditions; a few drops ofammonium hydroxide per 100 mL of elution solvent) gives the titlecompound, MS m/z (M+H)⁺=576.3.

Example 799 1-phenylcyclopropylamine (VI)

[1898] Following the procedure described in N.W. Werner et.al., J. Org.Syn. Coll. Vol. 5, 273-276, sodium azide (0.915g, 14.1 mmol) is slowlyadded to a solution of 1-phenyl-cyclopropanecarboxlic acid (1.0 g, 6.1mmol) in concentrated sulfuric acid (5 ml) and dichloromethane (10 ml).The sodium sulfate precipitated out of solution. The reaction mixture isheated to 50 degrees C. for 17 hours and then cooled to 0 degrees C. Themixture is basified to pH=11 with sodium hydroxide (lN) and extractedwith dichloromethane (2×). The organic layers are combined, dried oversodium sulfate, filtered and concentrated. The residue is purified bychromatography (silica gel; isopropyl alcohol/chloroform/ammoniumhydroxide 4/95/1) to give the title compound, MS (ESI+) for C₉H₁₁N m/z(M+H)⁺=134.

Example 800 7-methoxy-1,2,3,4-tetrahydro-1-naphthalenamine (VI)

[1899] 7-Methoxy-1-tetralone (2.0 g, 11.3 mmol), hydroxylaminehydrochloride (1.56 g, 22.6 mmol) and sodium acetate (1.8g, 22.6 mrnmol)are suspended in ethanol/water (3/1, 40 mL). The mixture is heated for45 min. at 100 degrees C. The mixture is allowed to cool overnight andthe precipitate obtained is filtered and washed with water to yield anintermediate oxime, MS (ES) (M+H): 192.1. The oxime is dissolved inglacial acetic acid (25 ml) and palladium/carbon (500 mg) is added andthe mixture hydrogenated under 50 psi at 20-25 degrees C. overnight. Thecatalyst is filtered over diatomaceous earth and washed with methanol.The combined filtrates are concentrated. The concentrate is trituratedwith ether to give the title compound, MS (CI) (MH+): 178.2.

Example 8013-Amino-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-methylbutanamidedihydrochloride

[1900] Following the general procedure of EXAMPLE 6 and makingnon-critical variations but starting with(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]4-phenyl-2-butanol (VIII) andreacting it with 3-[(tert-butoxycarbonyl)amino]-2-methylbutanoic acid(IX), and then treatment with HCl, the title compound is obtained, HRMScalculated =400.2600, observed=400.2596.

Example 802N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-ethylhexanamidehydrochloride

[1901] Following the general procedure of EXAMPLE 6 and makingnon-critical variations but starting with(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII) andreacting it with 2-ethylhexanoic acid (IX), the title compound isobtained, HRMS calculated=427.2961, observed=427.2961.

Example 803N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(isobutylsulfonyl)amino]propanamidetrifluoroacetate

[1902] Following the general procedure of CHART I and makingnon-critical variations but starting with(2R,3S)-3-amino-1-[(3-iodobenzyl)amino]-4-phenyl-2-butanol (VIII) andreacting it with N-(isobutylsulfonyl)-beta-alanine (IX), the titlecompound is obtained, HRMS calculated=588.1393, observed=588.1379.

Example 804N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³-(isobutylsulfonyl)-beta-alaninamidetrifluoroacetate

[1903] Following the general procedure of CHART I and makingnon-critical variations but starting with(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-iodobenzyl)amino]-2-butanol(VII) and reacting it with N-(isobutylsulfonyl)-beta-alanine (IX), thetitle compound is obtained, M+H=624.

Example 8055-bromo-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropylisophthalamidehydrochloride

[1904] Following the general procedure of EXAMPLE 6 and makingnon-critical variations but starting with(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-iodobetzyl)amino]-2-butanol(VIII) and reacting it with 3-bromo-5-[(dipropylamino)carbonyl]benzoicacid (IX), the title compound is obtained, M+H=745.

Example 806N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide

[1905] Following the general procedure of EXAMPLE 6 and makingnon-critical 5 variations but starting with(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1-phenylcyclopropyl)amino]-2-butanol(VIII) and reacting it with 3-[(dipropylamino)carbonyl]-5-methylbenzoicacid (IX), the substituted amine (X) is obtained. MH⁺=578.

Example 806.15-bromo-N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide

[1906] Following the general procedure of EXAMPLE 6 and makingnon-critical variations but starting with(2R,3S)-3-amino-1-[(3-bromobenzyl)amino]4-(3,5-15difluorophenyl)-2-butanol hydrochloride (VIII) and reacting it with3-bromo-5-[(dipropylamino)carbonyl]benzoic acid (IX), the title compoundis obtained, NMR (500 MHz, CD₃OD): δ 7.85, 7.72, 7.69, 7.67, 7.52, 7.51,6.88, 6.86, 6.74, 4.394.13, 3.95-3.88, 3.53-2.96, 2.82, 1.70, 1.50, 0.99and 0.71.

Examples 807-1,064

[1907] Following the general procedure of CHART A and EXAMPLES 4-6,321-327, 329-464, 466-527, 529-579, 597-619 and 633-708 and makingnon-critical variations, and using the appropriate amines (VIII) andamide forming agents (IX), the titled compounds are obtained. EXAMPLESubstituted Amine (X) 807N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(2-propylpentanoyl)benzamide808N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylpentanoyl)-5-methylbenzamide809N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide810N-{(1S,2R)-1-benzyl-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide811N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylbutanoyl)-5-methylbenzamide812N¹-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(2-propylpentanoyl)isophthalamide813N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylpentanoyl)-5-methylbenzamide814N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(2-propylpentanoyl)isophthalamide815N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]proyl}-5-(2-propylpentanoyl)isophthalamide816N-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propyl]-3-methyl-5-(2-propylpentanoyl)benzamide817N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(2-propylpentanoyl)benzamide818N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide819N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-pyridinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide820N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-pyridinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide821N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-propynyl)isophthalamide822N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diproyl-5-(1-propynyl)isophthalamide823N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-(2-propynyl)isophthalamide824N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(2-propynyl)isophthalamide825N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide826N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(3-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide827N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide828N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-butynyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide829N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide830N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(2-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide831N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide832N¹-{(1S,2R)-3-(benzylamino)-1-[4-(benzyloxy)benzyl]-2-hydroxypropyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide833N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide834N¹-[(1S,2R)-3-(benzylamino)-1-(cyclohexylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide835N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide836N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide8372,3,5-trideoxy-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-methoxybenzyl)amino]-1-S-phen-yl-1-thio-D-erythouro-pentitol 838N¹-[(1S,2R)-3-(benzylamino)-1-(3-furylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide839N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-5-methyl-N³,N³-dipropylisophthalamide840N¹-[(1S,2R)-3-(benzylamino)-1-(4-flouorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide841N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide842N¹-[(1S,2R)-3-(benzylamino)-1-(2-furylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide843N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide844N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-methylbutyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide845N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide846N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(4-hydroxybenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide847N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-butynyl)-5-methyl-N³,N³-dipropylisophthalamide848N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-butynyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide8495-(benzylamino)-2,3,5-trideoxy-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-1-S-phenyl-1-thio-D-erythouro-pentitol850N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide851N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(4-hydroxybenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide852N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide853N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-methylbutyl}-5-methyl-N³,N³-dipropylisophthalamide854N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide855*N¹-[(1S,2R)-3-(benzylamino)-1-(3-furylmethyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide856N¹-((1S)-1-[(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide857N¹-[(1S,2R)-3-(benzylamino)-1-(4-fluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide858N¹-[(1S,2R)-3-(benzylamino)-1-(2-furylmethyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide859N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide860N¹-{(1S,2R)-3-(benzylamino)-2-hydroxy-1-(1-naphthylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide861N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide862N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide863N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide864N¹-{(1S,2R)-3-(benzylamino)-1-[4-(benzyloxy)benzyl]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide865N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide866N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide867N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide868N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-butynyl}-5-methyl-N³,N³-dipropylisophthalamide869N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide870N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide871N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide872N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide873N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide874N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide875N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide876N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide877N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide878N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide879N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide880N¹-{(1S,2R)-1-hydroxy-1-[3-(hydroxymethyl)benzyl]-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide881N¹-{(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-[3-(hydroxymethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide882n¹-{(1S,2R)-2-hydroxy-1-[3-(hydroxymethyl)benzyl]-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide883N¹-{(1S,2R)-2-hydroxy-1-[4-(hydroxymethyl)benzyl]-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide884N¹-{(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-[4-(hydroxymethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide885N¹-{(1S,2R)-2-hydroxy-1-[4-(hydroxymethyl)benzyl]-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide886N¹-{(1S,2R)-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide887N¹-[(1S,2R)-3-[(3-ethylbenzyl)amino]-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide888N¹-{(1S,2R)-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide889N¹-{(1S,2R)-1-[3-(benzyloxy)-5-fluorobenzyl]-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide890N¹-{(1S,2R)-1-[3-(benzyloxy)-5-fluorobenzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide891N-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide892N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide8933-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]propanamide894N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide8953-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide896N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide8973-[(dipropylamino)sulfonyl]-N-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}propanamide898N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide8993-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide900N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide9013-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide902N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide9033-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]propanamide904N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide9053-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]propanamide906N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N⁵,N⁵-dipropyl-pentanediamide 907N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-{[(2R)-1-ethylpyrrolidinyl]carbo-nyl}-5-methylbenzamide 908N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-{[(2S)-2-ethylpyrrolidinyl]carbo-nyl}-5-methylbenzamide 909N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-ethyl-1H-imidazol-2-yl)carbo-nyl]-5-methylbenzamide 910N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-ethyl-4-methyl-1H-imidazol-5-yl)carbo-nyl]-5-methylbenzamide 911N¹((1S,2)-1-(3,5-difluorobenzyl)-2-hydroxy-2-{1-[(3-methoxybenzyl)amino]cyclopropyl}ethyl)-5-methyl-N³,N³-dipropylisophthalamide912N¹-((1S,2)-1-(3,5-difluorobenzyl)-2-{1-[(3-ethylbenzyl)amino]cyclopropyl}-2-hydroxyethyl)-5-methyl-N³,N³-dipropylisophthalamide913(1R,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2,3-cyclo-propanetricarboxamide 914(1R,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-phenyl-N²,N²-dipropyl-1,2-cyclo-propanedicarboxamide 915(1R,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-N²,N²-dipropyl-1,2-cyclo-propanedicarboxamide 916(1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-N²,N²-dipropyl-1,2-cyclo-propanedicarboxamide 917(1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-phenyl-N²,N²-dipropyl-1,2-cyclo-propanedicarboxamide 918(1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2,3-cyclo-propanetricarboxamide 919(1R,2R,3S)-3-(1-amino-2-oxoethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-di-propyl-1,2-cyclopropanedicarboxamide 920(1R,2R,3R)-3-(2-amino-2-oxoethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]-propyl}-N²,N²-di-propyl-1,2-cyclopropanedicarboxamide 921(1R,2R,3S)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxo-ethyl]-3-methylcyclopropanecarboxamide 922(1R,2R,3R)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxo-ethyl]-3-methylcyclopropanecarboxamide 923(1S,2R,3R)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxo-ethyl]-3-phenylcyclopropanecarboxamide 924(1S,2R,3S)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxo-ethyl]-3-phenylcyclopropanecarboxamide 925(1S,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[2-(dipropylamino)-2-oxo-ethyl]-1,2-cyclopropanedicarboxamide 926(1S,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[2-(dipropylamino)-2-oxo-ethyl]-1,2-cyclopropanedicarboxamide 927N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoro-methyl)sulfonyl]amino}isophthalamide 928N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sul-fonyl]amino}isophthalamide 929N¹-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide930N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-{methyl[(trifluoromethyl)sulfonyl]amino}-N³,N³-di-propylisophthalamide 931N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-{methyl[(trifluoromethyl)sulfonyl]a-mino}-N³,N³-dipropylisophthalamide 932N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{propyl[(trifluoromethyl)sul-fonyl]amino}isophthalamide 933N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsuflonyl)amino]-N³,N³-di-propylisophthalamide 934N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-di-propylisophthalamide 935N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide936N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide937N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethyalmino)benzyl]amino}-2-hydroxypropyl)-3-[(dipropylamino)sulfonyl]propanamide938N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-2-hydroxypropyl)-3-[(dipropylamino)sul-fonyl]propanamide 939N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-3-[(dipropyalmino)sul-fonyl]propanamide 940N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyl]amino}propyl)-3-[(dipropylamino)sulfonyl]propanamide941N-[(1S,2R)-3-[(3-cyclopropylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-[(dipropylamino)sulfonyl]propanamide942N¹-[(1S,2R)-3-[(3-cyclopropylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide943N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1,3-thiazol-2-yl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide944N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1,3-oxazol-2-yl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide945N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide946N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroyxpropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide947N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-(aminosulfonyl)-N³,N³-dipropylisophthalamide948N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-(methylsuflonyl)-N³,N³-dipropylisophthalamide949N¹-[(1S,2R)-3-{[3-(diethylamino)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide950N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-morpholinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide951N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-piperazinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide952N¹-[(1S,2R)-3-{[3-(aminosulfonyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide953N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({3-[(dimethylamino)sulfonyl]benzyl}amino)-2-hydroxypropyl]-5-meth-yl-N³,N³-dipropylisophthalamide 954N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-piperidinylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide955N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(methylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide956N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isopropylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide957N¹-[(1S,2R)-3-{[3-(aminocarbonyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide958N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({3-[(dimethylamino)carbonyl]benzyl}amino)-2-hydroxypropyl]-5-meth-yl-N³,N³-dipropylisophthalamide 959N¹-[(1S,2R)-3-[(3-cyanobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide9603-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}meth-yl)phenylcarbamate 9613-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)phenyldimethylcarbamate 962N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-propynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide963N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-methyl-1-butynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide964N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(2-propynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide965N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(5-isobutyl-1,3,4-oxadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 966N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 967N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(5-ethyl-1,3,4-thiadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 968N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(5-isobutyl-1,3,4-thiadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 969N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 970N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-isobutyl-1,2,4-thiadiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 971N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-isobutyl-1,2,4-oxadiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 972N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 973N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-oxazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 974N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-oxazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 975N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isobutyl-1,3,4-oxadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 976N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isobutyl-1,3,4-thiadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 977N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-1,3,4-thiadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-proylisophthalamide 978N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 979N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-proylisophthalamide 980N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 981N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-thiadiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 982N¹-((1S,2R)-1-(3,5-difluorbenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-oxadiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 983N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-2H-tetraazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 984N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-2H-tetraazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 985N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-4-pyridimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylisophthalamide 986N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isopropyl-4-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 987N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethynyl-4-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-di-propylsophthalamide 988N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-4-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 989N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[6-(dimethylamino)-4-pyrimidinyl]methyl}amino)-2-hydroxypropyl]-5-meth-yl-N³,N³-dipropylisophthalamide 990N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[2-(dimethylamino)-4-pyrimidinyl]methyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-di-propylisophthalamide 991N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[4-(dimethylamino)-2-pyrimidinyl]methyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-di-propylisophthalamide 992N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-isopropyl-2-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 993N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4-ethyl-2-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide994N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-3-pyridazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide995N³-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide996N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isopropyl-3-pyridazinyl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 997N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-propynyl)benzyl]amino}propyl)-N⁵,N⁵-diproyl-3,5-pyridinedicarboxamide998N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-4-pyridazinyl)methyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 999N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide1000N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(6-ethyl-4-pyridazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide1001N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide1002N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(6-ethyl-2-pyrazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide1003N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide1004N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isoproyl-2-pyrazinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide1005N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3,4,5-trifluorobenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1006N¹-((1S,2R)-2-hydroxy-1-(3,4,5-trifluorobenzyl)-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide1007N¹-((1S,2R)-2-hydroxy-1-(2,3,5,6-tetrafluorobenzyl)-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-di-propylisophthalamide 1008N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2,3,5,6-tetrafluorobenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1009N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-meth-yl-N³,N³-dipropylisophthalamide 1010N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-di-propyl-1,3,5-benzenetricarboxamide 1011N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1R,2S)-6-ethyl-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-2-hydroxypropyl)-5-meth-yl-N³,N³-dipropylisophthalamide 1012N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1R,2S)-6-ethyl-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-2-hydroxypropyl)-N³,N³-di-propyl-1,3,5-benzenetricarboxamide 1013N¹{(1S,2R)-2-hydroxy-1-(1H-indol-5-ylmethyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1014N¹-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(1H-indol-5-ylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1015N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1016N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1017N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide1018N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethyl)benzyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1019N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-pyridinylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1020N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-pyridinylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1021N¹-{(1S,2R)-1-[3-fluoro-5-(trifluoromethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-di-propylisophthalamide 1022N¹-{(1S,2R)-1-[3-fluoro-5-(trifluoromethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-di-propyl-1,3,5-benzenetricarboxamide 1023N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethoxy)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide1024N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethoxy)benzyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1025N¹-{(1S,2R)-2-hydroxy-1-(3-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1026N¹-{(1S,2R)-2-hydroxy-1-(3-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1027N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(4-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1028N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(4-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1029N¹-{(1S,2R)-1-(4-fluoro-3-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1030N¹-{(1S,2R)-1-(4-fluoro-3-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1031N¹-{(1S,2R)-1-(4-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1032N¹-{(1S,2R)-1-(4-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1033N¹-{(1S,2R)-2-hydroxy-1-(3-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1034N¹-{(1S,2R)-2-hydroxy-1-(3-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1035N¹-{(1S,2R)-2-hydroxy-1-(4-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1036N¹-{(1S,2R)-2-hydroxy-1-(4-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1037N¹-{(1S,2R)-1-(3-chloro-5-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1038N¹-{(1S,2R)-1-(3-chloro-5-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1039N¹-{(1S,2R)-1-(4-chloro-3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1040N¹-{(1S,2R)-1-(4-chloro-3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1041N¹-{(1S,2R)-1-(3,5-dichlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1042N¹-{(1S,2R)-1-(3,5-dichlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1043N¹-{(1S,2R)-1-[4-(dimethylamino)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1044N¹-{(1S,2R)-1-[4-(dimethylamino)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1045N¹-{(1S,2R)-1-(3-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1046N¹-{(1S,2R)-1-(3-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1047N¹-{(1S,2R)-1-(3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1048N¹-{(1S,2R)-1-(3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1049N¹-{(1S,2R)-2-hydroxy-1-(4-isopropylbenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1050N¹-{(1S,2R)-2-hydroxy-1-(4-isopropylbenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1051N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(6-methoxy-2-pyridinyl)methyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide1052N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(6-methoxy-2-pyridinyl)methyl]propyl}-N³,N³-di-propyl-1,3,5-benzenetricarboxamide 1053N¹-{(1S,2R)-2-hdyroxy-3-[(3-methoxybenzyl)amino]-1-[(5-methyl-2-pyridinyl)methyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide1054N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(5-methyl-2-pyridinyl)methyl]propyl}-N³,N³-dipropyl-1,3,5-benzene-tricarboxamide 1055N¹-{(1S,2R)-1-(3-fluoro-4-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1056N¹-{(1S,2R)-1-(3-fluoro-4-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1057N¹-{(1S,2R)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1058N¹-{(1S,2R)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1059N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-methoxy-5-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1060N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-methoxy-5-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1061N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1,3-thiazol-2-ylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide1062N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1,3-thiazol-2-ylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide1063N¹-{(1S,2R)-1-[(5-chloro-2-thienyl)methyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide1064N¹-{(1S,2R)-1-[(5-chloro-2-thienyl)methyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide

Examples 1,065-1,155

[1908] Following the general procedure of CHART A and EXAMPLES 4-6,321-327, 329-464,466-527, 529-579, 597-619 and 633-708 and makingnon-critical variations, and using the appropriate amines (VIII) andamide forming agents (IX), the titled compounds are obtained. EXAMPLESubstituted Amine (X) 1,065N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide1,066N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]1,3-thiazole-4-carboxamide 1,067N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,068N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(propylsulfonyl)amino]-1,3-thiazole-4-carboxamide1,069N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide1,070N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-thiazole-4-carboxamide1,071N-{(1S,2R)-1-benzy-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,072N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,073N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide 1,074N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,075N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,076N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,077N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide 1,078N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,079N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[3-methoxybenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,080N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,081N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-piperidinylcarbonyl)benzamide1,082N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(methylsulfonyl)amino]-l,3-oxazole-2-carboxamide1,083N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,084N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,085N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-piperidinylcarbonyl)benzamide1,086N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,087N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,088N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,089N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(4-morpholinylcarbonyl)benzamide1,090N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(ethylsulfonyl)amino]-1,3-oxazole-2-carboxamide1,091N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-2-[methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,092N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(ethylsulfonyl)amino]-1,3-oxazole-2-carboxamide1,093N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(4-morpholinylcarbonyl)benzamide1,094N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(propylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,095N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,096N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(methylsulfonyl)amino]-1,3-thiazole-2-carboxamide 1,097N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-piperazinylcarbonyl)benzamide1,098N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)amino]-1,3-thiazole-2-carboxamide1,099N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,100N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide1,101N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-piperazinylcarbonyl)benzamide1,102N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl]-4-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide 1,103N⁴-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4,5-dicarboxamide 1,104N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide 1,105N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methylisophthalamide1,106N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide 1,107N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,108N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[3-iodobenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide1,109 N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N³-methylisophthalamide 1,110N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methyl-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,111N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,112N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-methyl-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,113N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-ethyl-4-hydroxyisophthalamide1,114N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide 1,115N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,116N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-3-isoxazolecarboxamide1,117N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-4-hydroxyisophthalamide1,118N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-3-isoxazolecarboxamide1,119 N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,120N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(methylsulfonyl)amino]-5-isoxazolecarboxamide1,121N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³-ethyl-4-hydroxyisophthalamide1,122N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(methylsulfonyl)amino]-5-isoxazolecarboxamide1,123N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,124N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-(hydroxymethyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,125N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxyisophthalamide 1,1265-cyclopropyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,127N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,128N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-isopropyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,129N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxyisophthalamide 1,130N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,131N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,132N-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,133N-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide1,134N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-isobutylisophthalamide1,1352-{[(cyclopropylmethyl)sulfonyl]amino}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1,3-oxazole-4-carboxamide 1,136N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-isobutyl-N³-methylisophthalamide 1,137N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(isobutylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,138N3-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methylisophthalamide 1,139N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(isobutylsulfonyl)amino]-1,3-1,3-oxazole-4-carboxamide 1,140N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methyl-N³-propylisophthalamide 1,141N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(isobutylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,142N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N³-methyl-N³-propylisophthalamide 1,143N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(phenylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,144N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-ethyl-4-hydroxy-N³-propylisophthalamide 1,145N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-{[(4-methylphenyl)sulfony]amino}-1,3-oxazole-4-carboxamide 1,146N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-4-hydroxy-N³-propylisophthalamide 1,147N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-{[(4-methylphenyl)sulfonyl]amino}-1,3-oxazole-4-carboxamide 1,148N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(phenylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,149N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³,N³- dipropylisophthalamide 1,150N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,151N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N³,N³- dipropylisophthalamide 1,152N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide 1,153N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxy-N³,N³- dipropylisophthalamide 1,154N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide 1,155N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-thiazole-4-carboxamide

Examples 1,156-1,214

[1909] Following the general procedure of CHART A and EXAMPLES 4-6,321-327, 329-464, 466-527, 529-579, 597-619 and 633-708 and makingnon-critical variations, and using the appropriate amines (VIII) andamide forming agents (IX), the titled compounds are obtained. EXAMPLESubstituted Amine (X) MH+ 1,156N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-[propionyl(propyl)amino]benzamide532.5 1,157N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-butyl-1H-indole-5-carboxamideAnal. Found C = 73.58; H = 7.44; N = 8.24. 1,159N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyl(propionyl)amino]-5-methylbenzamide546.3 1,160N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-1-propyl-1H-indole-6-carboxamide500.3 1,161N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-(1-propylbutyl)-1H-indole-6-carboxamide542.2 1,162N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)methyl]amino}propyl)-5-methyl-573.3 N³,N³-dipropylisophthalamide 1,163N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyb-5-{[(trifluoromethyl)713.0 sulfonyl]amino}isophthalamide 1,1643-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]576.1 benzoic acid 1,165N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-prop-1-604.4 ynylisophthalamide 1,166N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-(dipropylamino)isonicotinamideHRMS [32 505.31 76 1,167N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,168N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(ethylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,169N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(propylsulfonyl)amino]isophthalamide 1,170N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(isopropylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,171N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(isobutylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,172N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide 1,173N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(2-furylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,174N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(1,3-thiazol-5-ylsulfonyl)amino]isophthalamide 1,175N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl-5-}(1,3-oxazol-5-ylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,176N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(1,3-oxazol-4-ylsulfonyl)amino]-N³,N³dipropylisophthalamide 1,177N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(1,3-thiazol-4-ylsulfonyl)amino]isophthalamide 1,178N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-{[(1-methyl-1H-[(1,3-thiazol-4-sulfonyl]amino}-N³,N³-dipropylisophthalamide 1,179N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(1,3-thiazol-4-N³dipropylisophthalamide 1,1805-{[(5-cyanopyridin-2-yl)sulfonyl[amino}-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2-hydroxypropyl}-N³,N³-dipropylisophthalamide 1,181N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-({[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}amino)isophthalamide 1,182N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}benzamide 1,183N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}amino)benzamide 1,1843-{[(5-cyanopyridin-2-yl)sulfonyl]amino}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide 1,185N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(phenylsulfonyl)amino]benzamide1,186N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3[(methylsulfonyl)amino]benzaamide1,187N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(ethylsulfonyl)amino]benzamide1,188N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(propylsulfonyl)amino]benzamide1,189N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(isobutylsulfonyl)amino]benzamide1,190N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(isopropylsulfonyl)amino]benzamide1,191N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(1-ethylpropyl)sulfonyl]amino}benzamide 1,1923-[(cyclohexylsulfonyl)amino]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide 1,193N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino)-2-hydroxypropyl}-3-{[(1-propylbutyl)sulfonyl]amino}benzamide 1,194N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(thien-2-ylsulfonyl)amino]benzamide 1,195 N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(2-furylsulfonyl)amino]benzamide 1,196N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(isoxazol-5-ylsulfonyl)amino]benzamide 1,197N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(isoxazol-3-ylsulfonyl)amino]benzamide 1,198N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-furylsulfonyl)amino]benzamide1,199 N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(thien-3-ylsulfonyl)amino]benzamide 1,200 N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,3-thiazol-4-ylsulfonyl)amino]benzamide 1,201N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,3-thiazol-5-ylsulfonyl)amino]enzamide 1,202N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,3-thiazol-2-ylsulfonyl)amino]benzamide 1,203N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide 1,204N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide 1,205N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-[(methylsulfonyl)amino]-N³,N3-dipropylisoplithalamide 1,206N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propy]-5-[methylsulfonyl)amino]-N³,N³-dipropylisophthalamide 1,207N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isophthalamide1,208N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide 1,2095-bromo-N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isophthalamide1,2103-tert-butoxy-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide1,2113-tert-butoxy-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide1,212N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide 1,213N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(trifluoromethoxy)benzamide1,214N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(trifluoromethoxy)benzamide

Examples 1,215-1,259

[1910] Following the general procedure of CHART A and EXAMPLES 4-6,321-327, 329-464, 466-527, 529-579, 597-619 and 633-708 and makingnon-critical variations, and using the appropriate amines (VIII) andamide forming agents (IX), the titled compounds are obtained. EXAM- PLESubstituted Amine (X) [M + H]+ 1,215N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3- 581.4iodobenzyl)amino]propyl}-2-hydroxy-2-(4- methylphenyl)acetamide 1,216N1-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 610.4[(3-iodobenzyl)amino]propyl}-4-hydroxy-N3- methylisophthalamide 1,217N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3- 642.4iodobenzyl)amino]propyl}-2-hydroxy-2-(4-methoxy- 3-nitrophenyl)acetamide1,218 5-(aminosulfonyl)-N-{(1S,2R)-1-(3,5-difluoro- 646.5benzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}- 2-methoxybenzamide1,219 N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3- 650.5iodobenzyl)amino]propyl}-4-hydroxy-3-(pyrrolidin- 1-ylcarbonyl)benzamide1,220 N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3- 621.4iodobenzyl)amino]propyl}-2-[(methyl-sulfonyl)amino]-1,3-oxazole-4-carboxamide 1,221N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 663.4[(3-methoxybenzyl)amino]propyl}-5-(3,5-dimethyl-isoxazol-4-yl)-N³,N³-dipropylisophthalamide 1,222N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 651.4[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide 1,2233-(cyclohexylcarbonyl)-N-{(1S,2R)-1-(3,5- 565.4difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide 1,224N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 540.4[(3-methoxybenzyl)amino]propyl}-5-methyl-N³- propylisophthalamide 1,2253-[cyclohexyl(hydroxy)methyl]-N-{(1S,2R)-1-(3,5- 567.4difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide 1,226N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 647.5ethylbenzyl)amino]-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N³,N³-dipropylisophthalamide 1,227N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 567ethylbenzyl)amino-1-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide 1,228N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 600{[(3-isobutyl-1,2,4-oxadiazol-5- yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 1,229N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 563ethynylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide 1,230N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 581[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropyl-pyridine-3,5-dicarboxamide 1,231N¹-[(1S,2R)-3-[(1-acetylpiperidin-4-yl)amino]-1- 587(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide 1,232N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 618[(3-pent-1-ynylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide 1,233N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 620{[3-(4-hydroxybut-1-ynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 1,234N¹-{3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 593ethylbenzyl)amino]-2-hydroxy- propyl}amino)carbonyl]-5-methylbenzoyl}-L-prolinamide 1,235 N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 538ethylbenzyl)amino]-2-hydroxypropyl}-N³-isopropyl- 5-methylisophthalamide1,236 N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 538ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³,5-dimethylisophthalamide 1,237N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 548ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-prop-2-ynylisophthalamide 1,238N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 552ethylbenzyl)amino]-2-hydroxypropyl}-N³-isobutyl- 5-methylisophthalamide1,239 N¹-(sec-butyl)-N₃-{(1S,2R)-1-(3,5-difluorobenzyl)- 5523-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5- methylisophthalamide 1,240N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 552ethylbenzyl)amino]-2-hydroxypropyl}-5- methylisophthalamide 1,241N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 552ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diethyl-5-methylisophthalamide 1,242N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 552ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-propylisophthalamide 1,243N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 552ethylbenzyl)amino]-2-hydroxypropyl}-N³-isopropyl-N³,5-dimethylisophthalamide 1,244N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 566ethylbenzyl)amino]-2-hydroxypropyl}-N¹,5- dimethylisophthalamide 1,245N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 566ethylbenzyl)amino]-2-hydroxypropyl}-N³-isobutyl-N³,5-dimethylisophthalamide 1,246N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 566ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-5-methyl-N³-propylisophthalamide 1,247N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 566ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³-isopropyl-5-methylisophthalamide 1,248N¹,N¹-diallyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)- 5763-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5- methylisophthalamide 1,2493-(azepan-1-ylcarbonyl)-N-{(1S,2R)-1-(3,5- 578difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide 1,250N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 580ethylbenzyl)amino)-2-hydroxypropyl}-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide 1,251N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 580ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide 1,252N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 580ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diisopropyl-5-methylisophthalamide 1,253N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 580ethylbenzyl)amino]-2-hydroxypropyl}-N¹-ethyl-5- methylisophthalamide1,254 N¹-(cyclopropylmethyl)-N³-{(1S,2R)-1-(3,5- 592difluorobenyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N¹-propylisophthalamide 1,2551-{3-[({(1S,2R)-1-(3,5-dlfluorobenzyl)-3-[(3- 593ethylbenzyl)amino]-2-hydroxy- propyl}amino)carbonyl]-5-methylbenzoyl}-D-prolinamide 1,256 N¹-cyclohexyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-592 3-[(3-ethylbenzyl)amino-2-hydroxypropyl}-N¹,5-dimethylisophthalamide 1,257N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 592{[1-(3-methylphenyl)cyclopropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide 1,258N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- 579(1,2,3,4-tetrahydronaphthalen-1-ylamino)propyl]-N⁵,N⁵-diisopropylpyridine-3,5-dicarboxamide 1,259N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3- 586.1ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide

[1911]

BIOLOGICAL EXAMPLES Example A

[1912] Enzyme Inhibition Assay

[1913] The compounds of the invention are analyzed for inhibitoryactivity by use of the MBP-C₁₂₅ assay. This assay determines therelative inhibition of beta-secretase cleavage of a model APP substrate,MBP-C125SW, by the compounds assayed as compared with an untreatedcontrol. A detailed description of the assay parameters can be found,for example, in U.S. Pat. No. 5,942,400. Briefly, the substrate is afusion peptide formed of maltose binding protein (MBP) and the carboxyterminal 125 amino acids of APP-SW, the Swedish mutation. Thebeta-secretase enzymne is derived from human brain tissue as describedin Sinha et.al, 1999, Nature 40:537-540) or recombinantly produced asthe full-length enzyme (amino acids 1-501), and can be prepared, forexample, from 293 cells expressing the recombinant cDNA, as described inWO00/47618.

[1914] Inhibition of the enzyme is analyzed, for example, by immunoassayof the enzyme's cleavage products. One exemplary ELISA uses an anti-MBPcapture antibody that is deposited on precoated and blocked 96-well highbinding plates, followed by incubation with diluted enzyme reactionsupernatant, incubation with a specific reporter antibody, for example,biotinylated anti-SW 192 reporter antibody, and further incubation withstreptavidin/alkaline phosphatase. In the assay, cleavage of the intactMBP-C125SW fusion protein results in the generation of a truncatedamino-terminal fragment, exposing a new SW-192 antibody-positive epitopeat the carboxy terminus. Detection is effected by a fluorescentsubstrate signal on cleavage by the phosphatase. ELISA only detectscleavage following Leu 596 at the substrate's APP-SW 751 mutation site.

[1915] Specific Assay Procedure:

[1916] Compounds are diluted in a 1:1 dilution series to a six-pointconcentration curve (two wells per concentration) in one 96-plate rowper compound tested. Each of the test compounds is prepared in DMSO tomake up a 10 millimolar stock solution. The stock solution is seriallydiluted in DMSO to obtain a final compound concentration of 200micromolar at the high point of a 6-point dilution curve. Ten (10)microliters of each dilution is added to each of two wells on row C of acorresponding V-bottom plate to which 190 microliters of 52 millimolarNaOAc, 7.9% DMSO, pH 4.5 are pre-added. The NaOAc diluted compound plateis spun down to pellet precipitant and 20 microliters/well istransferred to a corresponding flat-bottom plate to which 30 microlitersof ice-cold enzyme-substrate mixture (2.5 microliters MBP-C125SWsubstrate, 0.03 microliters enzyme and 24.5 microliters ice cold 0.09%TX100 per 30 microliters) is added. The final reaction mixture of 200micromolar compound at the highest curve point is in 5% DMSO, 20millimolar NaAc, 0.06% TX100, atppH 4.5.

[1917] Warming the plates to 37 degrees C. starts the enzyme reaction.After 90 minutes at 37 degrees C., 200 microliters/well cold specimendiluent is added to stop the reaction and 20 microliters/well istransferred to a corresponding anti-MBP antibody coated ELISA plate forcapture, containing 80 microliters/well specimen diluent. This reactionis incubated overnight at 4 degrees C. and the ELISA is developed thenext day after a 2 hours incubation with anti-192SW antibody, followedby Streptavidin-AP conjugate and fluorescent substrate. The signal isread on a fluorescent plate reader.

[1918] Relative compound inhibition potency is determined by calculatingthe concentration of compound that showed a fifty percent reduction indetected signal (IC₅₀) compared to the enzyme reaction signal in thecontrol wells with no added compound. In this assay, the compounds ofthe invention exhibited an IC₅₀ of less than 50 micromolar.

Example B

[1919] Cell Free Inhibition Assay Utilizing a Synthetic APP Substrate

[1920] A synthetic APP substrate that can be cleaved by beta-secretaseand having N-terminal biotin and made fluorescent by the covalentattachment of oregon green at the Cys residue is used to assaybeta-secretase activity in the presence or absence of the inhibitorycompounds of the invention. Useful substrates include the following:

[1921] Biotin-SEVNL-DAEFR[oregon green]KK [SEQ ID NO: 1]

[1922] Biotin-SEVKM-DAEFR[oregon green]KK [SEQ ID NO: 2]

[1923] Biotin-GLNIKTEEISEISY-EVEFRC[oregon green]KK [SEQ ID NO: 3]

[1924] Biotin-ADRGLTTRPGSGLTNIKTEEISEVNL-DAEF[oregon green]KK [SEQ IDNO:4]

[1925] Biotin-FVNQHLCoxGSHLVEALY-LVCoxGERGFFYTPKA[oregon green]KK [SEQID NO: 5]

[1926] The enzyme (0.1 nanomolar) and test compounds (0.001-100micromolar) are incubated in pre-blocked, low affinity, black plates(384 well) at 37 degrees C. for 30 minutes. The reaction is initiated byaddition of 150 millimolar substrate to a final volume of 30 microliterper well. The final assay conditions are: 0.001-100 micromolar compoundinhibitor; 0.1 molar sodium acetate (pH 4.5); 150 nanomolar substrate;0.1 nanomolar soluble beta-secretase; 0.001% Tween 20, and 2% DMSO. Theassay mixture is incubated for 3 hours at 37 degrees C., and thereaction is terminated by the addition of a saturating concentration ofimmunopure streptavidin. After incubation with streptavidin at roomtemperature for 15 minutes, fluorescence polarization is measured, forexample, using a LJL Acqurest (Ex485 nm/Em530 nm). The activity of thebeta-secretase enzyme is detected by changes in the fluorescencepolarization that occur when the substrate is cleaved by the enzyme.Incubation in the presence or absence of compound inhibitor demonstratesspecific inhibition of beta-secretase enzymatic cleavage of itssynthetic APP substrate. In this assay, compounds of the inventionexhibited an IC50 of less than 50 micromolar.

Example C

[1927] Beta-Secretase Inhibition: P26-P4′SW Assay

[1928] Synthetic substrates containing the beta-secretase cleavage siteof APP are used to assay beta-secretase activity, using the methodsdescribed, for example, in published PCT application WO/00/47618. TheP26-P4′SW substrate is a peptide of the sequence:(biotin)CGGADRGLTTRPGSGLTNIKTEEISEVNLDAEF [SEQ ID NO: 6] The P26-PIstandard has the sequence:

[1929] (biotin)CGGADRGLTTRPGSGLTNIKTEEISEVNL [SEQ ID NO: 7]

[1930] Briefly, the biotin-coupled synthetic substrates are incubated ata concentration of from about 0 to about 200 micromolar in this assay.When testing inhibitory compounds, a substrate concentration of about1.0 micromolar is preferred. Test compounds diluted in DMSO are added tothe reaction mixture, with a final DMSO concentration of 5%. Controlsalso contain a final DMSO concentration of 5%. The concentration of betasecretase enzyme in the reaction is varied, to give productconcentrations with the linear range of the ELISA assay, about 125 to2000 picomolar, after dilution.

[1931] The reaction mixture also includes 20 millimolar sodium acetate,pH 4.5, 0.06% Triton X100, and is incubated at 37 degrees C. for about 1to 3 hours. Samples are then diluted in assay buffer (for example, 145.4nanomolar sodium chloride, 9.51 millimolar sodium phosphate, 7.7millimolar sodium azide, 0.05% Triton X405, 6g/liter bovine serumalbumin, pH 7.4) to quench the reaction, then diluted further forimmunoassay of the cleavage products.

[1932] Cleavage products can be assayed by ELISA. Diluted samples andstandards are incubated in assay plates coated with capture antibody,for example, SW1 92, for about 24 hours at 4 degrees C. After washing inTTBS buffer (150 millimolar sodium chloride, 25 millimolar Tris, 0.05%Tween 20, pH 7.5), the samples are incubated with strepavidin-APaccording to the manufacturer's instructions. After a one hourincubation at room temperature, the samples are washed in TTBS andincubated with fluorescent substrate solution A (31.2 g/liter2-amino-2-methyl-1-propanol, 30 mg/liter, pH 9.5). Reaction withstreptavidin-alkaline phosphate permits detection by fluorescence.Compounds that are effective inhibitors of beta-secretase activitydemonstrate reduced cleavage of the substrate as compared to a control.

Example D

[1933] Assays Using Synthetic Oligopeptide-Substrates

[1934] Synthetic oligopeptides are prepared that incorporate the knowncleavage site of beta-secretase, and optionally detectable tags, such asfluorescent or chouromogenic moieties. Examples of such peptides, aswell as their production and detection methods are described in U.S.Pat. No. 5,942,400, herein incorporated by reference. Cleavage productscan be detected using high performnance liquid chromatography, orfluorescent or chromogenic detection methods appropriate to the peptideto be detected, according to methods well known in the art. By way ofexample, one such peptide has the sequence SEVNL-DAEF [SEQ ID NO: 8],and the cleavage site is between residues 5 and 6. Another preferredsubstrate has the sequence ADRGLTTRPGSGLTNIKTEEISEVNL-DAEF [SEQ ID NO:9], and the cleavage site is between residues 26 and 27.

[1935] These synthetic APP substrates are incubated in the presence ofbeta-secretase under conditions sufficient to result in beta-secretasemediated cleavage of the substrate. Comparison of the cleavage resultsin the presence of the compound inhibitor to control results provides ameasure of the compound's inhibitory activity.

Example E

[1936] Inhibition of Beta-Secretase Activity—Cellular Assay

[1937] An exemplary assay for the analysis of inhibition ofbeta-secretase activity utilizes the human embryonic kidney cell lineHEKp293 (ATCC Accession No. CRL-1573) transfected with APP751 containingthe naturally occurring double mutation Lys651Met52 to Asn651Leu652(numbered for APP751), commonly called the Swedish mutation and shown tooverproduce A beta (Citron et.al., 1992, Nature 360:672-674), asdescribed in U.S. Pat. No. 5,604,102.

[1938] The cells are incubated in the presence/absence of the inhibitorycompound (diluted in DMSO) at the desired concentration, generally up to10 micrograms/ml. At the end of the treatment period, conditioned mediais analyzed for beta-secretase activity, for example, by analysis ofcleavage fragments. A beta can be analyzed by immunoassay, usingspecific detection antibodies. The enzymatic activity is measured in thepresence and absence of the compound inhibitors to demonstrate specificinhibition of beta-secretase mediated cleavage of APP substrate.

Example F

[1939] Inhibition of Beta-Secretase in Animal Models of AD

[1940] Various animal models can be used to screen for inhibition ofbeta-secretase activity. Examples of animal models useful in theinvention include, but are not limited to, mouse, guinea pig, dog, andthe like. The animals used can be wild type, transgenic, or knockoutmodels. In addition, mammalian models can express mutations in APP, suchas APP695-SW and the like described herein. Examples of transgenicnon-human mammalian models are described in U.S. Pat. Nos. 5,604,102,5,912,410 and 5,811,633.

[1941] PDAPP mice, prepared as described in Games et.al., 1995, Nature373:523-527 are useful to analyze in vivo suppression of A beta releasein the presence of putative inhibitory compounds. As described in U.S.Pat. No. 6,191,166, 4 month old PDAPP mice are administered compoundformulated in vehicle, such as corn oil. The mice are dosed withcompound (1-30 mg/ml; preferably 1-10 mg/ml). After time, e.g., 3-10hours, the animals are sacrificed, and brains removed for analysis.

[1942] Transgenic animals are administered an amount of the compoundinhibitor formulated in a carrier suitable for the chosen mode ofadministration. Control animals are untreated, treated with vehicle, ortreated with an inactive compound. Administration can be acute, i.e.,single dose or multiple doses in one day, or can be chronic, i.e.,dosing is repeated daily for a period of days. Beginning at time 0,brain tissue or cerebral fluid is obtained from selected animals andanalyzed for the presence of APP cleavage peptides, including A beta,for example, by immunoassay using specific antibodies for A betadetection. At the end of the test period, animals are sacrificed andbrain tissue or cerebral fluid is analyzed for the presence of A betaand/or beta-amyloid plaques. The tissue is also analyzed for necrosis.

[1943] Animals administered the compound inhibitors of the invention areexpected to demonstrate reduced A beta in brain tissues or cerebralfluids and reduced beta amyloid plaques in brain tissue, as comparedwith non-treated controls.

Example G

[1944] Inhibition of A Beta Production in Human Patients

[1945] Patients suffering from Alzheimer's Disease (AD) demonstrate anincreased amount of A beta in the brain. AD patients are administered anamount of the compound inhibitor formulated in a carrier suitable forthe chosen mode of administration. Administration is repeated daily forthe duration of the test period. Beginning on day 0, cognitive andmemory tests are performed, for example, once per month.

[1946] Patients administered the compound inhibitors are expected todemonstrate slowing or stabilization of disease progression as analyzedby changes in one or more of the following disease parameters: A betapresent in CSF or plasma; brain or hippocampal volume; A beta depositsin the brain; amyloid plaque in the brain; and scores for cognitive andmemory function, as compared with control, non-treated patients.

Example H

[1947] Prevention of A Beta Production in Patients at Risk for AD

[1948] Patients predisposed or at risk for developing AD are identifiedeither by recognition of a familial inheritance pattern, for example,presence of the Swedish Mutation, and/or by monitoring diagnosticparameters. Patients identified as predisposed or at risk for developingAD are administered an amount of the compound inhibitor formulated in acarrier suitable for the chosen mode of administration. Administrationis repeated daily for the duration of the test period. Beginning on day0, cognitive and memory tests are performed, for exmple, once per month.

[1949] Patients administered the compound inhibitors are expected todemonstrate slowing or stabilization of disease progression as analyzedby changes in one or more of the following disease parameters: A betapresent in CSF or plasma; brain or hippocampal volume; amyloid plaque inthe brain; and scores for cognitive and memory function, as comparedwith control, non-treated patients.

[1950] While this invention has been described with respect to variousspecific examples and embodiments, it is to be understood that theinvention is not limited thereby and should only be construed byinterpretation of the scope of the appended claims.

1 9 1 12 PRT Artificial Sequence Synthetic 1 Ser Glu Val Asn Leu Asp AlaGlu Phe Arg Lys Lys 1 5 10 2 12 PRT Artificial Sequence Synthetic 2 SerGlu Val Lys Met Asp Ala Glu Phe Arg Lys Lys 1 5 10 3 22 PRT ArtificialSequence Synthetic 3 Gly Leu Asn Ile Lys Thr Glu Glu Ile Ser Glu Ile SerTyr Glu Val 1 5 10 15 Glu Phe Arg Cys Lys Lys 20 4 32 PRT ArtificialSequence Synthetic 4 Ala Asp Arg Gly Leu Thr Thr Arg Pro Gly Ser Gly LeuThr Asn Ile 1 5 10 15 Lys Thr Glu Glu Ile Ser Glu Val Asn Leu Asp AlaGlu Phe Lys Lys 20 25 30 5 32 PRT Artificial Sequence Synthetic 5 PheVal Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 1 5 10 15Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Ala Lys Lys 20 25 306 33 PRT Artificial Sequence Synthetic 6 Cys Gly Gly Ala Asp Arg Gly LeuThr Thr Arg Pro Gly Ser Gly Leu 1 5 10 15 Thr Asn Ile Lys Thr Glu GluIle Ser Glu Val Asn Leu Asp Ala Glu 20 25 30 Phe 7 29 PRT ArtificialSequence Synthetic 7 Cys Gly Gly Ala Asp Arg Gly Leu Thr Thr Arg Pro GlySer Gly Leu 1 5 10 15 Thr Asn Ile Lys Thr Glu Glu Ile Ser Glu Val AsnLeu 20 25 8 9 PRT Artificial Sequence Synthetic 8 Ser Glu Val Asn LeuAsp Ala Glu Phe 1 5 9 30 PRT Artificial Sequence Synthetic 9 Ala Asp ArgGly Leu Thr Thr Arg Pro Gly Ser Gly Leu Thr Asn Ile 1 5 10 15 Lys ThrGlu Glu Ile Ser Glu Val Asn Leu Asp Ala Glu Phe 20 25 30

We claim:
 1. A substituted amine of formula (X)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (H) —OH, (I) —C≡N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n-1)(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂),₁- by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuiryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-hterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)Rt-b where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where Rica and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)Rt-b where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) is as defined below; where R_(N) is: (I) R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: (A) —CO—, (B) —SO₂—, (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are —H or C₁-C₄ alkyl, (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from the group consisting of —O—, —S— and —NR′— and where R′ and R″ are as defined above, and (E) a single bond; where R_(N-1) is selected from the group consisting of: (A) R_(N-aryl) where R_(N-aryl) is phenyl, 1-naphthyl, 2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted with one, two or three of the following substituents which can be the same or different and are: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) —OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I, (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—OP(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R1 b where R_(1-a) and R_(1-b) are as defined above, (38) —(CH₂)₀4—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (B) —R_(N-heteroaryl) where R_(N-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where RNA4 is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of. (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄-N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(Naryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five of: —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C) R_(N-aryl)—W—R_(N-aryl), where R_(N-aryl) is defined as above, (D) R_(N-aryl)—W—R_(N-heteroaryl), where R_(N-aryl) and R_(N-heteroaryl) are as defined above, (E) R_(N-aryl)—W—R_(N-1-heterocycle), where R_(N-heterocycle) is defined as R_(1-heterocycle), is defined above, (F) R_(N-heteroaryl)—W—R_(N-aryl), where R_(N-aryl) and R_(n-heteroaryl) are as defined above, (G) R_(N-heteroaryl)—W—R_(N-heteroaryl), where R_(N-heteroaryl) is as defined above, (H) R_(N-hetroaryl)—W—R_(N-1-heterocycle), where R_(N-1-heterocycle) is as defined as R_(1-heterocycle) is as defined above, and where R_(N-heteroaryl) is as defined above, (I) R_(N-heterocycle)—W—R_(N-aryl), where R_(N-heterocycle) is as defined as R_(1-heterocycle) is defined and where R_(N-aryl) are as defined above, (J) R_(N-heterocycle)—W—R_(N-heteroaryl), where R_(N-heterocycle) is as defined as R_(1-heterocycle) as defined above and R_(N-heteroaryl) are as defined above, and (K) R_(N-heterocycle)—W—R_(N-1-heterocycle), where R_(N-heterocycle) and R_(N-heteroaryl) are as defined above, where W is (1) —(CH₂)₀₋₄—, (2) —O—, (3)—S(O)₀₋₂—, (4)-N(R_(N-5))- where R_(N-5) is as defined above, or (5) —CO-₁ (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally subsfitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl isoptionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, —Cl, (IV) —CO—(C₁-C₆ alkyl)—S—(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is as defined above, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, or —Cl, (V) —CO—CH(—CH₂)₀₋₂—O—R_(N-10))—(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)) where R_(N-aryl) and R_(N-heteroaryl) are as defined above, where R_(N-10) is selected from the group consisting of: (A) —H, (B) C₁-C₆ alkyl, (C) C₃-C₇ cycloalkyl, (D) C₂-C₆ alkenyl with one double bond, (E) C₂-C₆ alkynyl with one triple bond, (F) R_(1-aryl) where R_(1-aryl) is as defined above, and (G) R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above, or (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substituted with one or two substitutents selected from the group consisting of: (A) —(CH₂)₀₋₄—OH, (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy, (C) —(CH₂)₀₋₄—C₁-C₆ thioalkoxy, (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —(CH₂)₀₋₄—CO—RN₄ where R_(N-4) is as defined above, (G) —(CH₂)₀₋₄—SO₂—(C₁-C₈ alkyl), (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl, where R_(C) is: (I) —C₁-C₁₀ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) where R_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO-O—(C₁-C₄ alkyl), and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y) are —H, C₁-C₄ alkyl optionally substituted with one or two —OH, C₁-C₄ alkoxy optionally substituted with one, two, or three of: —F, —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, C₂-C₆ alkenyl containing one or two double bonds, C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-, and where R_(C-x) and R_(C-y) are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)— and R_(C-aryl) is the same as R_(N-aryl); (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) where R_(C-heteroaryl) is the same as R_(N-heteroaryl) and R_(C-x) and R_(C-y) are as defined above, (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where R_(C-aryl), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) where R_(C-heteroaryl), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl) where R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, and R_(C-heterocycle) is the same as R_(N-heterocycle), (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle) where R_(C-heteroaryl), R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) where R_(C-heterocycle) R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-hterocycle)—R_(C-heteroaryl) where R_(C-heterocycle), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle) where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) and R_(C-2) are the same or different and are selected from the group consisting of: (A) —H, (B) —C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ aLkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl), (F) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (G) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C-aryl) is as defined for R_(1-aryl), (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (I) —(C₁-C₄ alkyi)—R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (J) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (K) —R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—, —S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, and where R_(C-aryl) is as defined above, (N) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C-heteoayl) where R_(C-4) and R_(C-heteroaryl) are as defined above, and (O) —R_(C-aryl) where R_(C-aryl) is as defined above, and where R_(C-3) is the same or different and is: (A) —H, (B) —C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R₁b are as defined above, (E) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (F) —R_(C′-aryl) where R_(C′-aryl) is as defined above, (G) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (H) —R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (I) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as defined above, (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, or (K) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or different and are as defined above, (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the same or different and are as defined above, (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)) where R_(C-aryl) and R_(C-heteroaryl) are as defined above, (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) are as defined above where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR_(N-5), O, or S(═O)₀₋₂, and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two —C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, =O, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XX) C₂-C₁o alkenyl containing one or two double bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) C₂-C₁₀ alkynyl containing one or two triple bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, -C-=N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-aryl) where R_(C-aryl) is as defined above and R_(C-6) is —(CH₂)₀₋₄—OH, (XXII) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-heteroaryl) where R_(C-heteroaryl) and R_(C-6) is as defined above, (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl))—CO—O(C₁-C₄ alkyl) where R_(C-aryl) and R_(C-heteroaryl) are as defined above, (XXIV) —CH(—CH₂—OH)—CH(—OH)-phenyl-NO₂, (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH, (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂, (XXVIII) —H, or (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) and R_(1-b) are as defined above; or a pharmaceutically acceptable salt thereof.
 2. A substituted amine of formula (X) according to claim 1 where R₁ is: —(CH₂)₀₋₁—(R_(1-aryl)) —(CH₂)_(n1)—(R_(1-heteroaryl)) where R_(N) is: R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: —CO—, and —SO₂—, where R_(N-1) is selected from the group consisting of: —R_(N-aryl), and —R_(N-heteroaryl), or —CO—CH(—(CH₂)₀₋₂—O—R_(N-10))—(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)); where R_(C) is: —C₁-C8 alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)) -cyclopentyl or -cyclohexyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 3. A substituted amine of formula (X) according to claim 2 where R₁ is: —(CH₂)—(R_(1-aryl)), or —(CH₂)—(R_(1-heteroaryl)); where R₂ is —H; where R₃ is —H; where R_(N) is: R_(N-1)—X_(N)— where X_(N) is: —CO—, where R_(N-1) is selected from the group consisting of: —R_(N-aryl), —R_(N-heteroaryl), where R_(C) is: —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 4. A substituted amine of formula (X) according to claim 3 where R_(C) is: —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 5. A substituted amine of formula (X) according to claim 1 where R₁ is —(CH₂)—(R_(1-aryl)) where R_(1-aryl) is phenyl.
 6. A substituted amine of formula (X) according to claim 1 where R₁ is —(CH₂)—(R_(1-aryl)) where R_(1-aryl) is phenyl substituted with two —F.
 7. A substituted amine of formula (X) according to claim 6 where the —F substitution is 3,5-difluorobenzyl.
 8. A substituted amine of formula (X) according to claim 1 where R₂ is —H.
 9. A substituted amine of formula (X) according to claim 1 where R₃ is —H.
 10. A substituted amine of formula (X) according to claim 1 where R_(N) is R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one —CO—NR_(N-2)R_(N-3) where the substitution on phenyl is 1,3-.
 11. A substituted amine of formula (X) according to claim 10 where R_(N-2) and R_(N-3) are the same and are C₃ alkyl.
 12. A substituted amine of formula (X) according to claim 1 where R_(N) is R_(N-1)—X_(N)— where X_(N) is-CO—, where RN—, is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one Cl alkyl and with one —CO—NR_(N-2)R_(N-3) where the substitution on the phenyl is 1,3,5-.
 13. A substituted amine of formula (X) according to claim 12 where R_(N-2) and R_(N-3) are the same and are C₃ alkyl.
 14. A substituted amine of formula (X) according to claim 1 where R_(N) is R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-heteroaryl) where R_(N-heteroaryl) is substituted with one —CO—NR_(N-2)R_(N-3).
 15. A substituted amine of formula (X) according to claim 14 where R_(N-2) and R_(N-3) are the same and are —C₃ alkyl.
 16. A substituted amine of formula (X) according to claim 1 where R_(C) is: —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-aryl) is phenyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 17. A substituted amine of formula (X) according to claim 16 where R_(C) is: —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-aryl) is phenyl.
 18. A substituted amine of formula (X) according to claim 17 where phenyl is substituted in the 3-position or 3,5-positions.
 19. A substituted amine of formula (X) according to claim 16 where R_(C) is: —(CH₂)—R_(C-heteroaryl).
 20. A substituted amine of formula (X) according to claim 16 where R_(C) is: —(CH₂)—R_(C-heterocycle).
 21. A substituted amine of formula (X) according to claim 16 where R_(C) is: -cyclohexyl ring fused to a phenyl ring.
 22. A substituted amine of formula (X) according to claim 1 where the pharmaceutically acceptable salt is selected from the group consisting of salts of the following acids acetic, aspartic, benzenesulfonic, benzoic, bicarbonic, bisulfuric, bitartaric, butyric, calcium edetate, camsylic, carbonic, chlorobenzoic, citric, edetic, edisylic, estolic, esyl, esylic, formic, fumaric, gluceptic, gluconic, glutamic, glycollylarsanilic, hexamic, hexylresorcinoic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxynaphthoic, isethionic, lactic, lactobionic, maleic, malic, malonic, mandelic, methanesulfonic, methylnitric, methylsulfuric, mucic, muconic, napsylic, nitric, oxalic, p-nitromethanesulfonic, pamoic, pantothenic, phosphoric, monohydrogen phosphoric, dihydrogen phosphoric, phthalic, polygalactouronic, propionic, salicylic, stearic, succinic, sulfamic, sulfanilic, sulfonic, sulfuric, tannic, tartaric, teoclic and toluenesulfonic.
 23. A substituted amine of formula (X) according to claim 1 which is selected from the group consisting of: N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(ethylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(benzylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isopropylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-bydroxy-3-(4-toluidino)propyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methoxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, ethyl {[(3S)-3-({3-[(dipropylamino)carbonyl]benzoyl}amino)-2-hydroxy-4-phenylbutyl]amino}(phenyl)acetate, N¹-((1S)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]amino}propy)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-chlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(4-chlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-hydroxyethoxy)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-1-ylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(tetrahydro-2-furanylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,2-diethoxyethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(butylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(cyclohexylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(2-aminobenzyl)amino]-1-benzyl-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-pyridinylmethyl)amino]propyl}-N³N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-pyrrolidinyl)ethyl]amino}propyl)-N³N³-dipropylisophthalamide, N¹ {(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-butoxypropyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-isopropoxypropyl)amino]propyl}-N³N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-phenylpropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,3-dimethylbutyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-phenylbutyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(4-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-chlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(4-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-pyridinyl)ethyl]amino}propyl) -N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-pyridinylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,3-dimethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethoxy)benzyl] amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-chloro-6-phenoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,3-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dichlorobenzyl)amino]-2-hydroxypropyl}-N′,N-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-({2-[4-(aminosulfonyl)phenyl]ethyl}amino)-1-benzyl-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3,4,5-trimethoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,4-dimethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)aminoj-2-hydroxypropyl}-N₃,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-methylbenzyl)amino}propyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-phenylethyl]amino}propyl)-N³,N¹-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-(1-naphthyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-(1-naphthyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxy-3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dihydroxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-methylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-methylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(2-propynylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(2-fluorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(3-fluorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(4-fluorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(4-bromophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S)-1-benzyl-2-hydroxy-3-{[²-(³-methoxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(2,4-dichlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(3-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S)-1-benzyl-3-{[²-(2,5-dimethoxyphenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methylphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[(1R)-1-benzyl-2-hydroxyethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-morpholinyl)propyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propyl]_N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[²-(4-morpholinyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N^(l)-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxybutyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-thienyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxybutyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,4-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(4-tert-butylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-N³,N³- dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N¹-dipropylisophtlialamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1,1-dimethyl-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(ethylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isobutylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isobutylamino)-2-methyl-3-oxopropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[4-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-benzyl-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[2-(dimethylamino)ethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5-methyl-N³,N³ dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]butyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-2-(benzylamino)-1-methyl-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-1-phenylpropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1S)-2-(ethylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-2-oxo-1-phenylethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclohexylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3R,5S)-3,5-dimethoxycyclohexyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, dimethyl (1R,3S)-5-{[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylate, (1R,3S)-5-{[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylic acid, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-1-phenylpropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-chlorobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(2-propylpentyl)sulfonyl]benzamide, N¹-[(1S,2R)-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylpropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-[(2-thienylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyrazinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(1,3-benzodioxol-5-ylmethyl)amino]-1-benzyl-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N3,N 3-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N¹-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1,2,3,4-tetrahydro-1-naphthalenylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methoxy-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-chloro-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-fluoro-N³,N³-dipropylisophthalamide, N²-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-2,5-thiophenedicarboxamide, N⁴-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N²,N²-dipropyl-2,4-pyridinedicarboxamide, N⁴-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁶,N⁶dipropyl-4,6-pyrimidinedicarboxamide, N-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-(4-morpholinylcarbonyl)benzamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N¹-[(1S,2R)-3-{[(1R)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(pentylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-[(1S)-3-({2-[4-(aminosulfonyl)phenyl]ethyl}amino)-1-benzyl-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, 3-benzoyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}[1,1′-biphenyl]-3-carboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-(2-methoxyethyl)-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-ethoxybenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-naphthamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1R)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(l R)-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,3-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-4-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,5-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-fluoro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-2-ylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-(difluoromethoxy)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(5-methyl-2-pyrazinyl)methyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-bromo-4-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isobutoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-methyl-1,3-thiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-methyl-N³-propylisophthalamide, N²-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N¹-dipropyl-2,5-furandicarboxamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1,2-diphenylethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, isomer A, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, isomer B, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(dimethylamino)benzamide, N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-2-methyl-iH-benzimidazole-5-carboxamide, 3-(aminosulfonyl)-N-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-chlorobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-cyanobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-chloro-3-nitrobenzamide, methyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-nitrobenzoate, tert-butyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]phenylcarbamate, N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-9,1 0-dioxo-9,10-dihydro-2-anthrancenylcarboxamide, N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-1H-1,2,3-benzotriazole-6-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-(3-methyl-5-oxo4,5-dihydro-1H-pyrazol-1-yl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1H-indole-5-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3—methoxybenzyl)amino]propyl}-3-fluoro-5-(trifluoromethyl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(trifluoromethyl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-(butylamino)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(trifluoromethoxy)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-dimethoxybenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-dimethylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-difluorobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-dichlorobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-(benzyloxy)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1,3-benzodioxole-5-carboxamide, 3-(acetylamino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide, 4-(acetylamino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3,5-dimethyl4-isoxazolyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-phenylpropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-3-furanylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-propoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-hydroxy-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-methyl-1-(3-methylphenyl)ethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1S)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-5-methylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(1-benzofuran-2-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1R)-1-(3-bromophenyl)ethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyl(butyryl)amino]-5-methylbenzamide, N¹-{1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide, N³-{1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N¹,N¹-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-butyl-1H-indole-6-carboxamide, N¹-[(1S,2R)-3-anilino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, 5-bromo-N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methylpentanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methylpentanamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-hydroxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³,N³-dipropylisophthalamide hydrochloride, N^(l)-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 1-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide trifluroacetate, 5-(aminosulfonyl)-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-pyrrolidinylsulfonyl)isophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(dimethylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-methyl-3-(methylsulfonyl)propanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(methylsulfonyl)propanamide, 2-amino-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methylsulfonyl)pentanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N4-phenylsuccinamide, (3R)-N⁴-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2,2,3-trimethylbutanediamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl -3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl)}-4-oxo-4-(1-piperidinyl)butanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁴,N⁴-dipropylsuccinamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N5-phenylpentanediamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,3-dimethyl-4-oxo4-(1-piperidinyl)butanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-(isopentylsulfonyl)butanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl -2,2-dimethyl-N4,N⁴-dipropylsuccinamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl 4-[(dipropylamino)sulfonyl]butanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl 4-[(methylanilino)sulfonyl]butanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)aminopropyl}-3-[(methylanilino)sulfonyl]propanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}acetamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(isopentylsulfonyl)propanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(l -piperidinyl)pentanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide and N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(³-iodobenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-isobutyl-N³,N³-dipropylisophthalamide, N¹-{(S ,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-tert-butyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dimethyl-N⁵,N⁵-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-amino-1-benzyl-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-propyl-1,3,5-benzenetricarboxamide, N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-3-[butyryl(propyl)amino]-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,4-dimnethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-aminobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}octanamide, N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyllethyl}amino)propyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methylbenzamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1H-isoindol-3-ylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹,N¹-diallyl-5-chloro-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}isophthalamide, N¹,N¹-diallyl-1-(3,5-difluorobenzyl)-2-hydroxy-3-f(1-methyl-1-phenylethyl)amino]propyl}isophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}--N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{((S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5- methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-h[(4,5-dimethyl-2-furyl)methyl]amino}-2-hydpro pyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-l(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-5-methyl-N³,N³-dipropylisophtlhalamide, N¹-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(cyclopropylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-2-furanylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-oxo-3-azepanyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-methyl-2-furyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-di(2-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropenylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(hexylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzamide, methyl 4-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)benzoate, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-isoxazolylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, (1R,2R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{f[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, 4-(butyrylamino)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]benzamide, N¹-[(1S,2R)-3-[(3-amino-3-oxopropyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide 1-oxide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-oxabicyclo[2.2. 1]hept-2-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,54ifluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-methyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3R)-2-oxoazepanyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclobutylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(5-hexynylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(2-furyl)-1-methylethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(2-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(cyclohexylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzy1-3-(cyclopropylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-oxo-3-azepanyl)amino]propyl}-N³,N³-dipropylisophthalamide, N-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-(butylsulfonyl)benzamide, N¹-[(1S,2R)-1-benzyl-3-({2-[(2-ethylhexyl)oxy]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[1-(4-hydroxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(cycloheptylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-2-ylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(dimethylamino)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-naphthamide, N¹-[(1S,2R)-1-benzyl-3-({2-[({5-[(dimethylamino)methyl]-2-furyl}methyl)sulfanyl]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-({2-[(2-chloro-6-fluorobenzyl)sulfanyl]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[([1,1′-biphenyl]4-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1-naphthylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-imidazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-phenyl-1H-imidazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-imidazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl-4-chloro-1H-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamnide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-benzimidazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-hydroxy-1-naphthyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-oxol4H-chromen-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³ dipropylisophthalamide, N¹-[(1S,2R)-3-({[5-cyano-6-(methylsulfanyl)-2-pyridinyl]methyl}amino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, [5-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-2-fuiryl]methyl acetate, N¹-[(1S,2R)-3-[(1-benzofuiran-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, methyl 4-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1-methyl-1H-pyrrole-2-carboxylate, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({[1-(phenylsulfonyl)-1H-pyrrol-2-yl]methyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-pyrrol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(4-chloro-1-methyl-i H-pyrazol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-phenyl-1H-pyrazol-4-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(5-chloro-2-thienyl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-phenoxy-2-thienyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-quinolinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-quinolinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-indol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{1[(-benzyl- H-indol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(l -methyl-1H-indol-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[({1-[(4-methylphenyl)sulfonyl]-1H-indol-3-yl}methyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl-1H-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, methyl 3-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1H-indole-6-carboxylate, 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-amino)carbonyl]-5-[butyl(butyry)amino]benzyl diethyl phosphate, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(cyanomethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(hydroxymethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]-N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]aminopropyl)-5-ethynyl-N3N3-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(8-quinolinyl)isophthalamide, N^(3-—){(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl})4′-methoxy-N⁵,N⁵-dipropyl[l ,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[l ,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-l ,1′-biphenyl-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(3-thienyl)isophthalamide, N-{(1R,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide, N¹-(4-hydroxybutyl)-N³-{(1S)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N¹-propylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³-(3-hydroxypropyl)-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-methylphenyl)propyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹I-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1,3-dioxo-2-propyl-5-isoindolinecarboxamide, N-{(1R,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-bromo-5-methylbenzamide, 3-bromo-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N¹,N¹-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(2-furyl)-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3′,5,5 ′-trimethyl-1,1′-biphenyl-3-carboxamide, 3′-Acetyl-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl[1,1′-biphenyl]-3-carboxamide, 5 N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3′-methoxy-5-methyl[1,1′-biphenyl]-3-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl[1,1′-biphenyl]-3-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-10 methyl-5-(2-thienyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl) amino]propyl}-3-methyl-5-(3-thienyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methyl-5-(3-thienyl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-3-(3-thienyl)benzamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³,N⁵,N⁵-tetrapropylbenzene-1,3,5-tricarboxamide, N¹-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide, Ethyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoate, N¹-{(1S,2R)-2-Hydroxy-1-(4-hydroxybenzyl)-3-[(3-25 methoxybenzyl)amino]propyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 5-Amino-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(trifluoroacetyl)amino]isophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylcarbonyl)amino]isophthalamide, 5 N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methacryloylamino)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-5-[(2,2-dimethylpropanoyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide. N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methylthio)pentanamide, tert-butyl (2R,3S)-3-({3-[(dipropylamino)sulfonyl]- propanoyl}amino)-2-hydroxy-4-phenylbutyl(3-methoxybenzyl)carbamate N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-[propionyl(propyl)amino]benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-butyl-1H-indole-5-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-bromo-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyl(propionyl)amino]-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-1-propyl-1H-indole-6-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-1-(1-propylbutyl)-1H-indole-6-carboxamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoic acid, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-(dipropylamino)isonicotinamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-hydroxy-2-(4-methylphenyl)acetamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxy-N3-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-hydroxy-2-(4-methoxy-3-nitrophenyl)acetamide, 5-(aminosulfonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-methoxybenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxy-3-(pyrrolidin-1-ylcarbonyl)benzamide, N-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(3,5-dimethylisoxazol-4-yl)-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide, 3-(cyclohexylcarbonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³-propylisophthalamide, 3-[cyclohexyl(hydroxy)methyl]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N³,N³-dipropylisophthalamide N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-oxadiazol -5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-hydroxybut-1-ynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 1-{3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropy 1}amino)carbonyl]-5-methylbenzoyl}-L-prolinamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isopropyl-5-methylisophthalamide, Ni-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-prop-2-ynylisophthalamide, NN¹-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylben zyl)amino]-2-hydroxypropyl}-N¹-isobutyl-5-methylisophthalamide, N(sec-butyl)-N3- (S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-{((S,2R )-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N3-diethyl-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5dimethyl-N³,5-propylisophthalamide, N¹-(1S,2R)-1—(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-isopropyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R )-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isobutyl-N3,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino-2-hydroxypropyl}-N³-ethyl-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³-isopropyl-5-methylisophthalamide, N¹,N¹-diallyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, 3-(azepan-1-ylcarbonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)am ino]-2-hydroxypropyl}-5-methylbenzamide N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylben)amino]-2-hydroxypropyl}-N³,N³-diisopropyl-5-methylisophthalamide, N-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino-2-hydroxypropyl}-N¹-ethyl-5-methylisophthalamide, N¹-(cyclopropylmethyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N¹-propylisophthalamide, 1-{3-[({(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropy l}amino)carbonyl]-5-methylbenzoyl}-D-prolinamide, N¹-cyclohexyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N′,5-dimethylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-(3-methylphenyl)cycloprop yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1,2,3,4-tetrahydronaphthalen-1-ylamino)propyl]-N⁵,N⁵-diisopropylpyridine-3,5-dicarboxamide, and N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide.
 24. A substituted amine of formula (X) according to claim 23 which is selected from the group consisting of: N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N3-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-rlmethyl)amino-3-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-hydroxyetboxy)etbyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(2-aminobenzyl)amino]-1-benzyl-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]aminopropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1,1-dimethyl-2-oxoethyl]amino}propyl)-5-methyl-N ,N N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isobutylamino)-2-methyl-3-oxopropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-benzyl-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-1-[(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N. -{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-pyridinylmethyl)amino]propyl}-5-methyl-N ,N¹-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]butyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-irpyiohtaaide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclohexylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, (1R,3S)-5-{[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylic acid, N¹-[(1S,2R)-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³ N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-5-methyl-N N3-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylpropyl)amino]propyl}-5-methyl-N¹,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-thienylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino}propyl]-5-methyl-N N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyrazinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methoxy-N³,N³-dipropylisophthalamide N 1-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-chloro-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-fluoro-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}[1,1′-biphenyl]-3-carboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-(2-methoxyethyl)-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1R)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1R)-3-{[3,5-bis(trifluoroinethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-fluoro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-(difluoromethoxy)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-bromo-4-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-methyl-1,3-thiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-methyl-N³-propylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, isomer B, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-3-furanylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-propoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl}-5-hydroxy-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-methyl-1-(3-methylphenyl)ethyl]aminopropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1S)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-5-methylbenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1R)-1-(3-bromophenyl)ethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N¹,N¹-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-hydroxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³,N³-dipropylisophthalamide hydrochloride, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 5-(aminosulfonyl)-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-pyrrolidinylsulfonyl)isophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N-{((1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(dimethylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-tert-butyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-aminobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-bis(2-methoxyethyl)isophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4,5-dimethyl-2-furyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropenylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(hexylamino)-2-hydroxypropylj-5-methyl-N ,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-(3-methyl-5-oxo4,5-dihydro-1H-pyrazol-1-yl)benzamide, methyl 4-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)benzoate, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-isoxazolylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, (1R,2R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl)}N²,N²_dipropyl-1,2-cyclopropanedicarboxamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide 1-oxide, N¹-{(1S,2R)-1-(3, 5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-oxabicyclo[2.2. 1]hept-2-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-methyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(5-hexynylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(2-furyl)-1-methylethyl]amino)-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino)propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-[(1S,2R)-3-[([1,1′-biphenyl]4-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-imidazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-phenyl-1H-imidazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl4-chloro-1H-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-({[5-cyano-6-(methylsulfanyl)-2-pyridinyl]methyl}amino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, [5-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-2-furyl]methyl acetate, N¹-[(1S,2R)-3-[(1-benzofuran-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, methyl 4-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1-methyl-1H-pyrrole-2-carboxylate, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-pyrrol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(5-chloro-2-thienyl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-indol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1-benzyl-1H-indol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-indol-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl-1H-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, methyl 3-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl3 amino)-2-hydroxybutyl]amino}methyl)-1H-indole-6-carboxylate, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(cyanomethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(hydroxymethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethynyl-N³,N³4-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-methoxy-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide hydrochlonde, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[l ,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropy[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-l ,1′-biphenyl-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide, N-{(1R,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³-(3-hydroxypropyl)-5-methyl-N¹-propylisophthalamide, N-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl -5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³,N⁵,N⁵-tetrapropylbenzene-1,3,5-tricarboxamide, N¹-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N ₃N³-dipropylbenzene-1,3,5-tricarboxamide, ethyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoate, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 5-amino-N 1-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylcarbonyl)amino]isophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methacryloylamino)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methylthio)pentanamide, 3-amino-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-methylbutanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-ethylhexanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(isobutylsulfonyl)amino]propanamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³-(isobutylsulfonyl)-beta-alaninamide, 5-bromo-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, and N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-1(3-methoxybenzyl)amino}propylamino)carbonyl]-5-[(dipropylamino)carbonyl]benzoic acid, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]pro pyl}-4-hydroxy-3-(pyrrolidin-1-ylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]pro pyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(l ,3-thiazol-2-yl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³-propylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-oxadiazol -5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropy l}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-hydroxybut-1-ynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 1-{3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropy 1}amino)carbonyl]-5-methylbenzoyl}-L-prolinamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzy)amino]-2-hydroxypropyl}-N³isopropyl-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-prop-2-ynylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-isobutyl-5-methylisophthalamide, N¹-(sec-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diethyl-5-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isopropyl-N³,5-dimethylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isobutyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³-isopropyl-5-methylisophthalamide, N¹,N¹-diallyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, 3-(azepan-1-ylcarbonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diisopropyl-5-methylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N¹-ethyl-5-methylisophthalamide, N¹-(cyclopropylmethyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N¹-propylisophthalamide, N¹-cyclohexyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N′,5-dimethylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-(3-methylphenyl)cycloprop yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, and N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide.
 25. A substituted amine of formula (X) according to claim 1 which is selected from the group consisting of: N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylpentanoyl)-5-methylbenzamide, N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-benzyl-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl -3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylbutanoyl)-5-methylbenzamide, N¹-{(1S,2R)-1-benzyl-3- (3-ethylbenzyl)aminol -2-hydroxypropyl}-5-(2-propylpentanoyl)isophthalaide, N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylpentanoyl)-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(2-propylpentanoyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hiydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(2-propylpentanoyl)isophthalamide, N-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propyl]-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide, N¹-(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-pyridinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-pyridinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-(1-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-(2-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(2-propynyl)isophthalamide, N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(3-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-butynyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(2-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fuirylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-(benzylamino)-1-[4-(benzyloxy)benzyl]-2-hydroxypropyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(cyclohexylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 2,3,5-trideoxy-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-methoxybenzyl)amino]-1-S-phenyl-1-thio-D-erythro-pentitol, N¹-[(1S,2R)-3-(benzylamino)-1-(3-furylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(4-fluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(2-furylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-methylbutyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(4-hydroxybenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl -3-butynyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-butynyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 5-(benzylamino)-2,3,5-trideoxy-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-1-S-phenyl-1-thio-D-erythro-pentitol, N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(4-hydroxybenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-methylbutyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3-furylmethyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(4-fluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(2-furylmethyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(1-naphthylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹ {(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-3-(benzylamino)-1-[4-(benzyloxy)benzyl]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-butynyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)aminopropyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹ {(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-[3-(hydroxymethyl)benzyl]-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-[3-(hydroxymethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-[3-(hydroxymethyl)benzyl]-3-[(3-iodobenzyl)amino]propyl3-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-[4-(hydroxymethyl)benzyl]-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-[4-(hydroxymethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-[4-(hydroxymethyl)benzyl]-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-ethylbenzyl)amino]-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[3-(benzyloxy)-5-fluorobenzyl]-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[3-(benzyloxy)-5-fluorobenzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]propanamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}propanamide, N 1-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(2-fiirylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide, N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]propanamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]propanamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-{[(2R)-1-ethylpyrrolidinyl]carbonyl}-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-{[(2S)-1-ethylpyrrolidinyl]carbonyl}-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-ethyl-i H-imidazol-2-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-ethyl4-methyl-1H-imidazol-5-yl)carbonyl]-5-methylbenzamide, N¹-((1S,²S)-1-(3,5-difluorobenzyl)-2-hydroxy-2-{1-[(3-methoxybenzyl)amino]cyclopropyl}ethyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2S)-1-(3,5-difluorobenzyl)-2-{1-[(³-ethylbenzyl)amino]cyclopropyl}-²-hydroxyethyl)-5-methyl-N³,N³-dipropylisophthalamide, (1R,2R,3R)-N 1-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2,3-cyclopropanetricarboxamide, (1R,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-phenyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, methoxybenzyl)amino]propyl}-3-methyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-phenyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2,3-cyclopropanetricarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl)-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3R)-3-(2-amino-2-oxoethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-methylcyclopropanecarboxamide, (1R,2R,3R)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-methylcyclopropanecarboxamide, (1S,2R,3R)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-phenylcyclopropanecarboxamide, (1S,2R,3S)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-phenylcyclopropanecarboxamide, (1S,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[2-(dipropylamino)-2-oxoethyl]-1,2-cyclopropanedicarboxamide, (1S,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[2-(dipropylamino)-2-oxoethyl]-1,2-cyclopropanedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-{methyl[(trifluoromethyl)sulfonyl]amino}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-{methyl[(trifluoromethyl)sulfonyl]amino}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{propyl[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-³-[(dipropylamino)sulfonyl]propanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-3-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-²-hydroxypropyl)-3-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-3-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyl]amino}propyl)-3-[(dipropylamino)sulfonyl]propanamide, N-[(1S,²R)-3-[(3-cyclopropylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-[(dipropylamino)sulfonyl]propanamide, N¹-[(1S,²R)-3-[(3-cyclopropylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1,3-thiazol-2-yl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1,3-oxazol-2-yl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-(aminosulfonyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-(methylsulfonyl)-N³,N³-dipropylisophthalamide, 5 N¹-[(1S,2R)-3-{[3-(diethylamino)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-morpholinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-piperazinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N 1-[(1S,2R)-3-{[3-(aminosulfonyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({3-[(dimethylamino)sulfonyl]benzyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzy)-2-hydroxy-3-{[3-(l1-N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-piperidiylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isopropylsulfonyl)benzyl]aminopropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[3-(aminocarbonyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({3-[(dimethylamino)carbonyl]benzyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-cyanobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, 3-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)phenylcarbamate, 3-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl] amino}methyl)phenyl dimethylcarbamate, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-propynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-methyl-1-butynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(2-propynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(5-isobutyl-1,3,4-oxadiazol-2-yl)methyl0amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(5-ethyl-1,3,4-thiadiazol-2-yl) methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(5-isobutyl-1,3,4-thiadiazol-2-yl) methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(3-ethyl-1,2,4-thiadiazol-5-yl) methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-isobutyl-1,2,4-thiadiazol-5-yl) methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-isobutyl-1,2,4-oxadiazol-5-yl) methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(3-ethyl-1,2,4-oxadiazol-5-yl) methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-oxazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-oxazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isobutyl-1,3,4-oxadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isobutyl-1,3,4-thiadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-1,3,4-thiadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-—thiadiazol-5-yl)methyl]amino}propyl)-5-mty-3N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-oxadiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-2H-tetraazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-2H-tetraazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N 1-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-4-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isopropyl4-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethynyl4-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-4-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[6-(dimethylamino)4-pyrimidinyllmethyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[2-(dimethylamino)-4-pyrimidinyllmethyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[4-(dimethylamino)-2-pyrimidinyl]methyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-isopropyl-2-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4-ethyl-2-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-[(5-ethyl-3-pyridazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isopropyl-3-pyridazinyl)methyl] aminol}propyl)-5-methyl-N³,N3-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-propynyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl4-pyridazinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(6-ethyl-4-pyridazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(6-ethyl-2-pyrazinyl)methyl] amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-2-pyrazinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3,4,5-trifluorobenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-2-hydroxy-1-(3,4,5-trifluorobenzyl)-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-2-hydroxy-1-(2,3,5,6-tetrafluorobenzyl)-3-{[3-* ? (trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2,3,5,6-tetrafluorobenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1R,2S)-6-ethyl-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1R,2S)-6-ethyl-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-2-hydroxypropyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(S,2R)-2-hydroxy-1-(1H-indol-5-ylmethyl)-3-[(3-methoxybenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(1H-indol-5-ylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethyl)benzyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-pyridinylmethyl)propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-pyridinylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[3-fluoro-5-(trifluoromethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[3-fluoro-5-(trifluoromethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethoxy)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethoxy)benzyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{((S,2R)-2-hydroxy-1-(3-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(3-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(4-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(4-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-fluoro-3-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-fluoro-3-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹ {(1S,2R)-1-(4-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(3-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(3-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-2-hydroxy-1-(4-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹N¹-{(1S,2R)-1-(3-chloro-5-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(I1S,2R)-1-(3-chloro-5-fluorobenzy)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-chloro-3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-chloro-3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹ {(1S,2R)-1-(3,5-dichloro robenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-dichloro benzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[4-(dimethylamino)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[4-(dimethylamino)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-isopropylbenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-isopropylbenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzy)amino]-1-[(6-methoxy-2-pyridinyl)methyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(6-methoxy-2-pyridinyl)methyllpropyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N, .-(S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(5-methyl-2-pyridinyl)methyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(5-methyl-2-pyridinyl)methyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-21d-(3x-fluoro4-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-(3hfluoro4-methylbenzyl)-2-hydroxy -3-[(3-methoxybelt)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro4-methoxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-methoxy-5-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-methoxy-5-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1,3-thiazol-2-ylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1,3-thiazol-2-ylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[(5-chloro-2-thienyl)methyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[(5-chloro-2-thienyl)methyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(propylsulfonyl)amino]-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-²-hydroxypropyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-²-hydroxypropyl)-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]nyl)a}mino]-,3-oxazole4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(³-ethylphenyl)cyclopropyl]amino}-²-hydroxypropyl)4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-²-[(methylsulfonyl)amino]-1,³-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,³-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-piperidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(methylsulfonyl)amino]-1-,3-oxazole-2-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl -2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)}4-hydroxy-3-(1-piperidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)aminol-2-hydroxypropyl}-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(4-morpholinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(ethylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}⁴-[(ethylsulfonyl)amino]-1,³-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(4-morpholinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(propylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(methylsulfonyl)amino]- I ,3-thiazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-piperazinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)amino]-1,3-thiazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5difluorobenzyl)-3-[(3-ethylbenzyl)aminol-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-piperazinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N⁴-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4,5-dicarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methyl-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-methyl-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-ethyl-4-hydroxyisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-3-isoxazolecarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl4-hydroxyisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-⁵-[(methylsulfonyl)amino]-3-isoxazolecarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(methylsulfonyl)amino]-5-isoxazolecarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³-ethyl-4-hydroxyisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(methylsulfonyl)amino]-5-isoxazolecarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzy1)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-(hydroxymethyl)-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxyisophthalamide, 5-cyclopropyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(propylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-isopropyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxyisophthalamide, N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(propylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-[(1S,²R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-isobutylisophthalamide, 2-{[(cyclopropylmethyl)sulfonyl]amino}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-³-[(³-ethylbenzyl)amino]-2-hydroxypropyl}-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-isobutyl-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(isobutylsulfonyl)amino]-1,³-oxazole-4-carboxamide, N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-²-[(isobutylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁴-hydroxy-N³-methyl-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(isobutylsulfonyl)amino]-1,³-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N3-methyl-N3-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(phenylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N3-ethyl-4-hydroxy-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-{[(4-methylphenyl)sulfonyl]amino}-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-ethyl4-hydroxy-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-{[(⁴-methylphenyl)sulfonyl]amino}-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(phenylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³, N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[methyl(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenizyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-hydroxy-N³, N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[methyl(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}4-hydroxy-N³, N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-thiazole4-carboxamide, N¹-.(.S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2 hydroxypropyl})-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(ethylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(propylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(isopropylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(isobutylsulfonyl)amino]-N3 N3-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁵-[(²-furylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenz1l)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(1,³-thiazol-5-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(1,3-oxazol-5-ylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(1,3-oxazol-4-ylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(1,³-thiazol-⁴-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}-N³ N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide, 5-{[(5-cyanopyridin-2-yl)sulfonyl]amino}-N¹-{(1S,2R)-1-(3,5-diluorobenzyl)-3-[(3-ethylbezyl)amino]-2-hydroxypropyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-*-hydroxypropyl}-N³,N³-dipropyl-5-(f{[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}amino)isophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(1-methyl-1H-imidazol4-yl)sulfonyl]amino}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}amino)benzamide, 3-{[(5-cyanopyridin-2-yl)sulfonyl]amino}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-³-[(³-ethylbenzyl)amino]-2-hydroxypropyl}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(phenylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(methylsulfonyl)aminolbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(ethylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(propylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(isobutylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(isopropylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(1-ethylpropyl)sulfonyl]amino}benzamide, 3-[(cyclohexylsulfonyl)amino]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(1-propylbutyl)sulfonyl]amino}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(thien-2-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(²-furylsulfonyl)amino]benzamide, hydroxypropyl}-³-[(isoxazol-5-ylsulfonyl)aminojbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(isoxazol-3-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(³-furylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(thien-3-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(t,3-hiazo-4-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,3-thiazol-5-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,³-thiazol-2-ylsulfonyl)amino]benzamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbnzyl aaino]-2-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isophthalamide, N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, 5-bromo-N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isophthalamide, 3-tert-butoxy-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide, 3-tert-butoxy-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(trifluoromethoxy)benzamide, and N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(trifluoromethoxy)benzamide.
 26. A protected compound of the formula (III)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NRt aR_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (H) —OH, (I) —C_N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n1)—(R_(1-heteroaryl)) where nli is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl -N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C_N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR -aR_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C═N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, -C—N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl)) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)RL b where RIa and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R2-1 is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) is as defined below; where X₁ is —Cl, —Br, —I, —O-tosylate, —O-mesylate, or —O-nosylate; where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxy carbonyl , 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobomyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.
 27. A protected compound of formula (III) according to claim 26 where R₁ is: —CH₂—(R_(1-aryl)), or —CH₂—(R_(1-heteroaryl)).
 28. A protected compound of formula (III) according to claim 27 where R_(1-aryl) is phenyl.
 29. A protected compound of formula (III) according to claim 28 where phenyl is substituted with one, two or three —F, —Cl, —Br or —I.
 30. A protected compound of formula (III) according to claim 29 where phenyl is substituted with one or two —F.
 31. A protected compound of formula (III) according to claim 30 where phenyl is substituted with two —F in the 3- and 5-positions giving 3,5-difluorophenyl.
 32. A protected compound of formula (III) according to claim 26 where R₂ and R₃ are both —H.
 33. A protected compound of formula (III) according to claim 26 where PROTECTING GROUP is t-butoxycarbonyl.
 34. A protected compound of formula (III) according to claim 26 where PROTECTING GROUP is benzyloxycarbonyl.
 35. A protected compound of formula (HII) according to claim 26 where X₁ is —Cl or —Br.
 36. A protected compound of formula (III) according to claim 26 which is selected from the group consisting of: tert-butyl (1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate, tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate, benzyl (1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate and benzyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate.
 37. An alcohol of the formula (IV)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-hetroaryl) where R_(1-heteroaryl) is as defined above, (H) —OH, (I) —C≡N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR,aR_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n1)—(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH -C-=N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (8) —OH, (9) —C_N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NRi,aR_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR,-aR_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (8) —OH, (9) —C-EN, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)Rl,b where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, -CE-N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NRlIRIb where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) is as defined above; where X₁ is —Cl, —Br, —I, —O-tosylate, —O-mesylate, or —O-nosylate; where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.
 38. An alcohol of formula (IV) according to claim 37 where R₁ is: —CH₂—(R_(1-aryl)), or —CH₂—(R_(1-heteroaryl)).
 39. An alcohol of formula (IV) according to claim 38 where R_(1-aryl) is phenyl.
 40. An alcohol of formula (IV) according to claim 39 where phenyl is substituted with one, two or three —F, —Cl, —Br or —I.
 41. An alcohol of formula (IV) according to claim 40 where phenyl is substituted with one or two —F.
 42. An alcohol of formula (IV) according to claim 41 where phenyl is substituted with two —F in the 3- and 5-positions giving 3,5-difluorophenyl.
 43. An alcohol of formula (IV) according to claim 37 where R₂ and R₃ are both —H.
 44. An alcohol of formula (IV) according to claim 37 where PROTECTING GROUP is 1-butoxycarbonyl.
 45. An alcohol of formula (IV) according to claim 37 where PROTECTING GROUP is benzyloxycarbonyl.
 46. An alcohol of formula (IV) according to claim 37 where X₁ is —Cl or —Br.
 47. An alcohol of formula (IV) according to claim 37 which is selected from the group consisting of: tert-butyl (1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, tert-butyl (1S,2S)-3-chloro-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, benzyl (1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate and benzyl (1S,2S)-3-chloro-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate.
 48. An epoxide of the formula (V)

where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀O— C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —ClC₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl), and (k) R_(1-heteroaryl), where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—) —H, where R₁ is: —CH₂-phenyl where -phenyl is substituted with two —F, —(CH₂)_(n1)—R_(1-heteroaryl) or —(CH₂)_(n1)—R_(1-heterocycle).
 49. An epoxide of formula (V) according to claim 48 where R₁ is: —(CH₂)_(n1)—(R_(1-heteroaryl)).
 50. An epoxide of formula (V) according to claim 48 where n₁ is
 1. 51. An epoxide of formula (V) according to claim 48 where R₁ is: —(CH₂)_(n1)—(R_(1-heterocycle)).
 52. An epoxide of formula (V) according to claim 51 where n₁ is
 1. 53. An epoxide of formula (V) according to claim 48 where phenyl is substituted in the 3- and 5-positions giving 3,5-difluorophenyl.
 54. An epoxide of formula (V) according to claim 48 where R₂ and R₃ are both —H.
 55. An epoxide of formula (V) according to claim 48 where PROTECTING GROUP is t-butoxycarbonyl.
 56. An epoxide of formula (V) according to claim 48 where PROTECTING GROUP is benzyloxycarbonyl.
 57. An epoxide of formula (V) according to claim 48 which is selected from the group consisting of: tert-butyl (1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate, and benzyl (1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiranyl]ethylcarbamate.
 58. A protected alcohol of the formula (VII)

where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀4—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R1,b where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R1 b where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above; where R_(C) is: (I) —C₁-C₁₀ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, -S(═O)₀₋₂ R_(1-a) where R_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO-O—(C₁-C₄ alkyl), and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y) are —H, C₁-C₄ alkyl optionally substituted with one or two —OH, C₁-C₄ alkoxy optionally substituted with one, two, or three of: —F, —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, C₂-C₆ alkenyl containing one or two double bonds, C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-, and where R_(C-x) and R_(C-y) are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)— and R_(C-aryl) is the same as R_(N-aryl); (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) and R_(C-x) and R_(C-y) are as defined above, (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) and R_(C-2) are the same or different and are selected from the group consisting of: (A) —H, (B) —C₁-C₆ allkyl, optionally substituted with one, two or three substituents selected from the group consisting Of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as definedabove, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) a re as defined above, (D) C₂-C₆ alkyyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —CON, —CF₃, CH—C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl), (F) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (G) —(C₁-C₄ alkyl)—Rca,,yi, (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl), (I) —(C₁-C₄ alkyl)—R_(C-heterocycle), (J) —R_(C-heteroaryl), (K) —R_(C-heterocycle), (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—, —S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, (N) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) is as defined above, and (O) —R_(C′-aryl), and where R_(C-3) is the same or different and is: (A) —H, (B) —C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where Rica and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (F) —R_(C′-aryl), (G) —R_(C-heteroaryl), (H) —R_(C-heterocycle), (I) —(C₁-C₄ alkyl)—R_(C′-aryl), (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl), or (K) —(C₁-C₄ alkyl)—R_(C-heterocycle), (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or different, (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the same or different, (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)), (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR_(N-5), O, or S(═O)₀₋₂, and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two —C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, ═O, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XX) C₂-C₁₀ alkenyl containing one or two double bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) C₂-C₁₀ alkynyl containing one or two triple bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXII) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-heteroaryl) where R_(C-6) is as defined above, (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl))—CO—O(C₁-C₄ alkyl), (XXIV) —CH(—CH₂—OH)—CH(—OH)-phenyl-NO₂, (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH, (XXVII) —CH₂—N—H—CH₂—CH(—O—CH₂—CH₃)₂, (XXVIII) —H, or (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) and R_(1-b) as are as defined above; or a pharmaceutically acceptable salt thereof. where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H. where R₁ is: —CH₂-phenyl where -phenyl is substituted with two —F, —(CH₂)_(n1)—R_(1-heteroaryl) and —(CH₂)_(n1)—R_(1-hterocycle), chemically acceptable salts thereof.
 59. A protected alcohol of formula (VII) according to claim 58 where R₁ is: —(CH₂)_(n1)—(R_(1-heteroaryl)).
 60. A protected alcohol of formula (VII) according to claim 59 where n₁ is
 1. 61. A protected alcohol of formula (VII) according to claim 58 where R₁ is: —(CH₂)_(n1)—(R_(1-heterocycle)).
 62. A protected alcohol of formula (VII) according to claim 61 where n₁ is
 1. 63. A protected alcohol of formula (VII) according to claim 58 where phenyl is substituted in the 3- and 5-positions giving 3,5-difluorophenyl.
 64. A protected alcohol of formula (VII) according to claim 58 where R₂ and R₃ are both —H.
 65. A protected alcohol of formula (VII) according to claim 58 where PROTECTING GROUP is t-butoxycarbonyl.
 66. A protected alcohol of formula (VII) according to claim 58 where PROTECTING GROUP is benzyloxycarbonyl.
 67. A protected alcohol of formula (VII) according to claim 58 where R_(C) is: —H, —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) are as defined in claim
 1. 68. A protected alcohol of formula (VII) according to claim 67 where R_(C) is: —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 69. A protected alcohol of formula (VII) according to claim 68 where R_(C) is: —C₁-C₈ alkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 70. A protected alcohol of formula (VII) according to claim 58 which is selected from the group consisting of: tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(ethylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(benzylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(tert-butylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-methylbenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methoxyphenyl)ethyl]amino}propylcarbamate tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate, ethyl ({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}amino)(phenyl)acetate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-(hydroxymethyl)-2-phenylethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2-chlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(4-chlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-hydroxyethoxy)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-1-ylamino)-2-hydroxypropylcarbamate tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxypropyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(tetrahydro-2-furanylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2,2-diethoxyethyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(pentylamino)propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(cyclohexylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-pyridinylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-3-[(2-aminobenzyl)amino]-1-benzyl-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-pyridinylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-pyrrolidinyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3-butoxypropyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-isopropoxypropyl)amino]propylcarbamate tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-phenylpropyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-methoxyethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenoxyethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-propoxyethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,3-dimethylbutyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-phenylbutyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-nitrobenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3-chlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(4-chlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-pyridinyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-pyridinylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2,3-dimethylbenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethoxy)benzyl] amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2-chloro-6-phenoxybenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethyl)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2,3-dichlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,5-dichlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethoxy)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-3-{[4-(aminosulfonyl)benzyl]amino}-1-benzyl-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-methoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-methylbenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3,4,5-trimethoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2,4-dimethoxybenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,4-dichlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(4-fluorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-methylbenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(l R)-1-phenylethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-phenylethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethyl)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-(1-naphthyl)ethyl]amino}propyl carbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-(1-naphthyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxy-3-methoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,4-dihydroxybenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-methylethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-methylethyl] amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(²-propynylamino)propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[²-(2-fluorophenyl)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[2-(3-fluorophenyl)ethyl] amino}-2-—hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[²-(⁴-fluorophenyl)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[²-(⁴-bromophenyl)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(3-methoxyphenyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[²-(²,⁴-dichlorophenyl)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[²-(3-chlorophenyl)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[²-(2,6-dimethoxyphenyl)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methylphenyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[(1R)-1-benzyl-2-hydroxyethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-morpholinyl)propyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-³-[(3,3-dimethylbutyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-morpholinyl)ethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(1-hydroxypropyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-thienylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxybutyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-phenylethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2,4-dichlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-phenylethyl]amino}propylcarbamate tert-butyl (1S,2R)-1-benzyl-3-[(3-tert-butylbenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(1-phenylethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropylcarbamate, methyl 7- t [(2R,3S)-3-[(tert-butoxycarbonyl)amino]4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}heptanoate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1,1-dimethyl-2-oxoethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-2-oxoethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]propyl}amino)propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]propyl}amino)propylcarbamate, tert-butyl (1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-3-(ethylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isobutylamino)propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isobutylamino)-2-methyl-3-oxopropyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-3-{[4-(dimethylamino)benzyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-3-{[(iS)-1-benzyl-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]-3-methylbutyl}amino)propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[2-(dimethylamino)ethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-pyridinylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-3-{[(1S)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(i -methyl-1-phenylethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]-3-methylbutyl}amino)propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]butyl}amino)propylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(i S)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylethyl)amino]propylcarbamate, tert-butyl (1S,2R)-3-{[2-(benzylamino)-1-methyl-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[1S)-2-(benzylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1S)-2-(ethylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-(isobutylamino)-2-oxo-1-phenylethyl] amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(cyclohexylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-(butylamino)-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-{[(3R,5S)-3,5-dimethoxycyclohexyl]amino}-2-hydroxypropylcarbamate, dimethyl (1R,3S)-5-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy4-phenylbutyl}amino)-1,3-cyclohexanedicarboxylate, (1R,3S)-5-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}amino)-1,3-cyclohexanedicarboxylic acid, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-phenylpropyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3-chlorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylpropyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-thienylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(2-pyrazinylmethyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-3-[(1,3-benzodioxol-5-ylmethyl)amino]-1-benzyl-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(2-furylmethyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3-fluorobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-isopropoxybenzyl)amino]propylcarbamate, tert-butyl (1S,2R)-1-benzyl-3-[(3-bromobenzyl)amino]-2-hydroxypropylcarbamate, tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propylcarbamate, and tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propylcarbamate.
 71. An amine of the formula (VIII)

where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR-,aR_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R1 b are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR,,aR_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂-i is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH2, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above; where R_(C) is: (I) —C₁-C₁₀ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) where R_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO—O—(C₁-C₄ alkyl), and —NRlaR_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y) are —H, C₁-C₄ alkyl optionally substituted with one or two —OH, C₁-C₄ alkoxy optionally substituted with one, two, or three of: —F, —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, C₂-C₆ alkenyl containing one or two double bonds, C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-, and where R_(C-x) and R_(C-y) are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)— and R_(C-aryl) is the same as R_(N-aryl); (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) where R_(C-heteroaryl) is the same as R_(N-heteteroaryl) and R_(C-x) and R_(C-y) are as defined above, (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where, R_(C-x) and R_(C-y) are as defined above, (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle) where, R_(C-x) and R_(C-y) are as defined above, (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where, R_(C-x) and R_(C-y) are as defined above, (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) and R_(C-2) are the same or different and are selected from the group consisting of: (A) —H, (B) —C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₁ ₂—S(O)₀₋₂—(C₁-C₆ alkyl), (F) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (G) —(C₁-C₄ alkyl)—R_(C′-aryl), (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl), (I) —(C₁-C₄ alkyl)—R_(C-heterocycle), (J) —R_(C-heteroaryl), (K) —R_(C-heterocycle), (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—, —S— or —NR_(C-5) where R_(C-5) is C₁-C₆ alkyl, and where R_(C-aryl) is as defined above, (N) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) is as defined above, and (O) —R_(C-aryl), and where Rc3 is the same or different and is: (A) —H, (B) —C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (F) —R_(C′-aryl), (G) —R_(C-heteroaryl), (H) —R_(C-heterocycle), (I) —(C₁-C₄ alkyl)—R_(C′-aryl), (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl), or (K) —(C₁-C₄ alkyl)—R_(C-heterocycle), (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or different, (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the same or different, (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)), (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR_(N-5), O, or S(═O)₀₋₂, and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two -C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, ═O, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XX) C₂-C₁₀ alkenyl containing one or two double bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) C₂-C₁₀ alkynyl containing one or two triple bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-aryl) where R_(C-aryl) is as defined above and R_(C-6) is —(CH₂)₀₋₆—OH, (XXII) —(C H₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-R_(C-heteroaryl) where R_(C-6) is as defined above, (XXIII) —CH(—R_(C-aryl) or R_(C-heteroary))—CO—O(C₁-C₄ alkyl), (XXIV) —CH(—CH₂—OH) —CH(—OH)-phenyl-NO₂, (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH, (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂, (XXVIII) —H, or (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) and R_(1-b) are as defined above; and where R₁ is: —CH₂-phenyl where -phenyl is substituted with two —F, —(CH₂)_(n1)—R_(1-heteroaryl) or —(CH₂)_(n1)—R_(1-heterocycle), and chemically acceptable salts thereof.
 72. An amine of formula (VIII) according to claim 71 where R₁ is: —(CH₂)_(n1)—(R_(1-heteroaryl)).
 73. An amine of formula (VIII) according to claim 72 where n₁ is
 1. 74. An amine of formula (VIII) according to claim 71 where R₁ is: —(CH₂)n₁—(R_(1-heterocycle)).
 75. An amine of formula (VIII) according to claim 74 where n₁ is
 1. 76. An amine of formula (VIII) according to claim 71 where phenyl is substituted in the 3- and 5-positions giving 3,5-difluorophenyl.
 77. An amine of formula (VIII) according to claim 71 where R₂ and R₃ are both —H.
 78. An amine of formula (VIII) according to claim 71 where R_(C) is: —H, —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 79. An amine of formula (VIII) according to claim 78 where R_(C) is: —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 80. An amine of formula (VIII) according to claim 79 where R_(C) is: —C₁-C₈ alkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 81. An amine of formula (VIII) according to claim 71 which is selected from the group consisting of: (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol, (2R,3S)-3-amino-1-(ethylamino)-4-phenyl-2-butanol, (2R,3S)-3-amino-1-(benzylamino)-4-phenyl-2-butanol, (2R,3S)-3-amino-1-(isopropylamino)-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(4-methylbenzyl)amino]-4-pheny1-2-butanol, (2R,3S)-3-amino-1-{[2-(4-methoxyphenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]4-phenyl-2-butanol, ethyl {[(2R,3S)-3-amino-2-hydroxy4-phenylbutyl]amino}(phenyl)acetate, (2R,3S)-3-amino-4-phenyl-1-[(2-phenylethyl)amino]-2-butanol, (2S)-2-{[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}-1-(4-nitrophenyl)-1,3-propanediol, (2R,3S)-3-amino-1-[(2-chlorobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(4-chlorobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(2-hydroxyethoxy)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-(2,3-dihydro-1H-inden-1-ylamino)-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(2-hydroxypropyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(tetrahydro-2-furanylmethyl)amino]-2-butanol, (2R,3S)-3-amino-1-[(2,2-diethoxyethyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-(butylamino)4-phenyl-2-butanol, (2R,3S)-3-amino-1-(cyclohexylamino)4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(2-pyridinylmethyl)amino]-2-butanol, (2R,3S)-3-amino-1-[(2-aminobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(3-pyridinylmethyl)amino]-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[2-(1-pyrrolidinyl)ethyl]amino}-2-butanol, (2R,3S)-3-amino-1-[(2-hydroxy-2-phenylethyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3-butoxypropyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3-isopropoxypropyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-(isopentylamino)-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(3-phenylpropyl)amino]-2-butanol, (2R,3S)-3-amino-1-[(2-methoxyethyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(2-phenoxyethyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(2-propoxyethyl)amino]-2-butanol, (2R,3S)-3-amino-1-[(3,3-dimethylbutyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(4-phenylbutyl)amino]-2-butanol, (2R,3S)-3-amino-1-[(3-iodobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(4-nitrobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3-chlorobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(4-chlorophenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[2-(2-pyridinyl)ethyl]amino}-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(4-pyridinylmethyl)amino]-2-butanol, (2R,3S)-3-amino-1-{[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(2,3-dimethylbenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[2-(trifluoromethoxy)benzyl]amino}-2-butanol, (2R,3S)-3-amino-1-[(2-chloro-6-phenoxybenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[4-(trifluoromethyl)benzyl]amino}-2-butanol, (2R,3S)-3-amino-1-[(2,3-dichlorobenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3,5-dichlorobenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3,5-difluorobenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[4-(trifluoromethoxy)benzyl]amino}-2-butanol, 4-({[(2R,3S)-3-amino-2-hydroxy4-phenylbutyl]amino}methyl)benzenesulfonamide, (2R,3S)-3-amino-1-[(4-methoxybenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(4-methylbenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(3,4,5-trimethoxybenzyl)amino]-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethoxy)benzyl]amino}-2-butanol, (2R,3S)-3-amino-1-[(3,5-dimethoxybenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(2,4-dimethoxybenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[([1,1′-biphenyl]-3-ylmethyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(3,4-dichlorobenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(2-fluorobenzyl)amino]4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanol, (2R,3S)-3-amino-1-[(2-methylbenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[(1R)-1-phenylethyl]amino}-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[(1S)-1-phenylethyl]amino}-2-butanol, (2R,3S)-3-amino-1-{[3,5-bis(trifluoromethyl)benzyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[2-(trifluoromethyl)benzyl]amino}-2-butanol, (2R,3S)-3-amino-1-{[(1S)-1-(1-naphthyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[(1R)-1-(1-naphthyl)ethyl]amino}-4-phenyl-2-butanol, 4-({[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}methyl)-2-methoxyphenol, 4-({[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino}methyl)-1,2-benzenediol, (2R,3S)-3-amino-1-[(3-methoxypropyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(I R)-2-hydroxy-1-methylethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[(1S)-2-hydroxy-1-methylethyl]amino}4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-(2-propynylamino)-2-butanol, (2R,3S)-3-amino-1-{[2-(2-fluoropheny1)ethyl]aminol -4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(3-fluorophenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-=-[2-(4-fluorophenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(4-bromophenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(3-methoxyphenyl)ethyl]aminol-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(2,4-dichorophenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(3-chmorophenyl)ethyl]amino}4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(2,5-dimethoxyphenyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(4-methylphenyl)ethyl]amino}-phenyl-2-butanol, (2R,3S)-3-amino-1-{[(1R)-1-benzyl-2-hydroxyethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[3-(4-morpholinyl)propyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-(isobutylamino)4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[2-(4-morpholinyl)ethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(2-hydroxybutyl)amino]-2-butanol, (2R,3S)-3-amino-4-phenyl-1-{[2-(2-thienyl)ethyl]amino)-2-butanol, 4-{[(2R,3S)-3-amino-2-hydroxy4-phenylbutyl]amino)-1-butanol, (2R,3S)-3-amino-1-{[(1S)-2-hydroxy-1-phenylethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(2,4-dichlorobenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-1-{[(1R)-2-hydroxy-1-phenylethyl]amino}-4-phenyl-2-butanol, (2R,3S)-3-amino-1-[(4-tert-butylbenzyl)amino]-4-phenyl-2-butanol, (2R,3S)-3-amino-4-phenyl-1-[(1-phenylethyl)amino]-2-butanol, (1R,2S)-1-{[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]amino)-2,3-dihydro-1H-inden-2-ol, (2R,3S)-3-amino-1-[(3,4-dimethylbenzyl)amino]-4-phenyl-2-butanol, methyl 7-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}heptanoate, 2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylpropanamide, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino)-N-isobutylpropanamide, 2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-2-methylpropanamide, 2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylacetamide, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylbutanamide, (2R)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylbutanamide, (2R,3S)-3-amino-1-(benzylamino)4-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-(ethylamino)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-(isobutylamino)-2-butanol, 3-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-2-methylpropanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[4-(dimethylamino)benzyl] amino)-2-butanol (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-3-phenylpropanamide, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-3-methylbutanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[2-(dimethylamino)ethyl]amino}-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-pyridinylmethyl)amino]-2-butanol, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-3-(benzyloxy)-N-isobutylpropanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1-methyl-1-phenylethyl)amino]-2-butanol, (2R)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-3-methylbutanamide, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutylpentanamide, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-3-hydroxy-N-isobutylpropanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-phenylethyl)amino]-2-butanol, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-benzylpropanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[(1S)-1-phenylpropyl]amino}-2-butanol, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-ethylpropanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol, (2S)-2-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-N-isobutyl-2-phenylethanamide, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-(isopentylamino)-2-butanol, (2R,3S)-3-amino-1-(cyclohexylamino)4-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-1-(butylamino)4-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxypropyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-hydroxy-2-phenylethyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[(3R,5S)-3,5-dimethoxycyclohexyl]amino}-2-butanol, dimethyl (1R,3S)-5-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}l -1,3-cyclohexanedicarboxylate, (1R,3S)-5-{[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylic acid, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[(1R)-1-phenylpropyl]amino}-2-butanol, (2R,3S)-3-amino-1-[(3-chlorobenzyl)amino]4-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol, (2R,3S)-3-amino-1-[([1,1′-biphenyl]-3-ylmethyl)amino]-4-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-odobenzyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methylbenzyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-phenylpropyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1,3-thiazol-5-ylmethyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-thienylmethyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(5-methoxy-1,2,3,4-tetrahydro-l1-naphthalenyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-pyrazinylmethyl)amino]-2-butanol, (2R,3S)-3-amino-4-[(3,5-difluorobenyl1)amino]4-(3-,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-(3,-[(1,3-benzodioxol-5-ylmethylm yl)amino-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3,5-dimethoxybenzyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(2-furylmethyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethoxy)benzyl]amino}-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-fluorobenzyl)amino]-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-isopropoxybenzyl)amino]-2-butanol, (2R,3S)-3-amino-1-[(3-bromobenzyl)amino]4-(3,5-difluorophenyl)-2-butanol, (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(5-methyl-2-furylmethyl)amino]-2-butanol, and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]-2-butanol.
 82. A protected ketone of formula (XI)

where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R₁b are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR,-aR_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NRI.aR_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above; where R_(C) is: (I) —C₁-C₁₀ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) where R_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO—O—(C₁-C₄ alkyl), and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y) are —H, C₁-C₄ alkyl optionally substituted with one or two —OH, C₁-C₄ alkoxy optionally substituted with one, two, or three of: —F, —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, C₂-C₆ alkenyl containing one or two double bonds, C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-, and where R_(C-x) and R_(C-y) are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—; (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) where R_(C-x) and R_(C-y) are as defined above, (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl) where R_(C-x) and R_(C-y) are as defined above, (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where R_(C-x) and R_(C-y) are as defined above, (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) and R_(C-2) are the same or different and are selected from the group consisting of: (A) —H, (B) —C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, -C-=N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl), (F) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (G) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl), (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl), (I) —(C₁-C₄ alkyl)—R_(C-heterocycle), (J) —R_(C-heteroaryl), (K) —R_(C-heterocycle), (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—, —S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, (N) —(CH₂)14—R_(C-4)—(CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) is as defined above, and (O) —R_(C′-aryl), and where R_(C-3) is the same or different and is: (A) —H, (B) —C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where RIca and R_(1-b) are as defined above, (F)—R_(C′-aryl), (G) R_(C-heteroaryl), (H) —R_(C-heterocycle), (I) —(C₁-C₄ alkyl)—R_(C′-aryl), (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl), or (K) —(C₁-C₄ alkyl)—R_(C-heterocycle), (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or different, (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the same or different, (XVIII) —CH(R_(C-aryl))(R_(C-hetetoaryl)), (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fuised to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR_(N-5), O, or S(═O)₀₋₂, and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two —C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, ═O, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XX) C₂-C₁₀ alkenyl containing one or two double bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) C₂-C₁₀ alkynyl containing one or two triple bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-aryl) R_(C-6) is —(CH₂)₀₋₆—OH, (XXII) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-heteroaryl) and R_(C-6) is as defined above, (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl))—CO—O(C₁-C₄ alkyl), (XXIV) —CH(—CH₂—OH)—CH(—OH)-phenyl-NO₂, (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH, (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂, (XXVIII) —H, or (XXIX) —(CH₂)₀₋₄—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) and R_(1-b) are as defined above; and where R₁ is: —CH₂-phenyl where -phenyl is substituted with two —F, —(CH₂)_(n1)—R_(1-heteroaryl) or —(CH₂)n₁—R_(1-heterocycle), where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop 1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.
 83. A protected ketone of formula (XI) according to claim 82 where R₁ is: —(CH₂)_(n1)—(R_(1-heteroaryl)).
 84. A protected ketone of formula (XI) according to claim 83 where n₁ is
 1. 85. A protected ketone of formula (XI) according to claim 82 where R₁ is: —(CH₂)_(n1)—(R_(1-heterocycle)).
 86. A protected ketone of formula (XI) according to claim 85 where n₁ is
 1. 87. A protected ketone of formula (XI) according to claim 82 where phenyl is substituted in the 3- and 5-positions giving 3,5-difluorophenyl.
 88. A protected ketone of formula (XI) according to claim 82 where R₂ and R₃ are both —H.
 89. A protected ketone of formula (XI) according to claim 82 where PROTECTING GROUP is t-butoxycarbonyl.
 90. A protected ketone of formula (XI) according to claim 82 where PROTECTING GROUP is benzyloxycarbonyl.
 91. A protected ketone of formula (XI) according to claim 82 where R_(C) is: —H, —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) are as defined above.
 92. A protected ketone of formula (XI) according to claim 91 where R_(C) is: —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-hcterocycle), or -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 93. A protected ketone of formula (XI) according to claim 92 where R_(C) is: —C₁-C₈ alkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 94. A protected ketone of formula (XI) according to claim 82 which is tert-butyl (1S)-1-(3,5-difluorobenzyl)-3-[(3-methoxybenzyl)amino]-2-oxopropylcarbamate.
 95. A protected azide of formula (XII)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl).
 103. A protected azide of formula (XII) according to claim 95 where PROTECTING GROUP is benzyloxycarbonyl.
 104. A protected azide of formula (XII) according to claim 95 which is: tert-Butyl-(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate, or benzyl-(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate.
 105. A protected amine of formula (XIII)

where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above; where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H; and where R₁ is: —CH₂-phenyl where -phenyl is substituted with two —F, —(CH₂)_(n1)—R_(1-heteroaryl), —(CH₂)_(n1)—R_(1-heterocycle).
 106. A protected amine of formula (XIII) according to claim 105 where R₁ is: —(CH₂)_(n1)—(R_(1-heteroaryl)).
 107. A protected amine of formula (XIII) according to claim 106 where n₁ is
 1. 108. A protected amine of formula (XIII) according to claim 105 where R₁ is: —(CH₂)_(n1)—(R_(1-heterocycle)).
 109. A protected amine of formula (XIII) according to claim 108 where n₁ is
 1. 110. A protected amine of formula (XIII) according to claim 105 where phenyl is substituted in the 3- and 5-positions giving 3,5-difluorophenyl.
 111. A protected amine of formula (XIII) according to claim 105 where R₂ and R₃ are both —H.
 112. A protected amine of formula (XIII) according to claim 105 where PROTECTING GROUP is t-butoxycarbonyl.
 113. A protected amine of formula (XIII) according to claim 105 where PROTECTING GROUP is benzyloxycarbonyl.
 114. A protected amine of formula (XIII) according to claim 105 which is tert-butyl (1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate.
 115. An unprotected azide of formula (XIV)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a), and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR, aR_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (H) —OH, (I) —C≡N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n-1)—(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cimnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n-1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (II) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n1)—(R_(1-hetrocycle) where n) ₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide, and homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C═N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) is as defined above; where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzy1oxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobornyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.
 116. An unprotected azide of formula (XIV) according to claim 115 where R₁ is: —CH₂—(R_(1-aryl)), or —(CH₂—(R_(1-heteroaryl)).
 117. An unprotected azide of formula (XIV) according to claim 116 where R_(1-aryl) is phenyl.
 118. An unprotected azide of formula (XMV) according to claim 117 where phenyl is substituted with one, two or three —F, —Cl, —Br or —I.
 119. An unprotected azide of formula (XIV) according to claim 118 where phenyl is substituted with one or two —F.
 120. An unprotected azide of formula (XIV) according to claim 119 where phenyl is substituted with two -F in the 3- and 5-positions giving 3,5-difluorophenyl.
 121. An unprotected azide of formula (XIV) according to claim 1115 where R₂ and R₃ are both —H.
 122. An unprotected azide of formula (XIV) according to claim 115 which is (2R,3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-butanol.
 123. An azide of formula (XV)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC—O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (H) —OH, (I) —C═N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where Ria and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n1)—(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j)—R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —OH, (9) —C_N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n-1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) is as defined above, where PROTECTING GROUP is selected from the group consisting of t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, acetyl, trichloroacetyl, dichloroacetyl, chloroacetyl, trifluoroacetyl, difluoroacetyl, fluoroacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4-xenyl)isopropoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl, 1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methylcyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)etboxycarbonyl, 2-(methylsulfonyl)ethoxycarbonyl, 2-(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobomyloxycarbonyl and 1-piperidyloxycarbonyl, 9-fluorenylmethyl carbonate, —CH—CH═CH₂ and phenyl-C(═N—)—H.
 96. A protected azide of formula (XII) according to claim 95 where R₁ is: —CH₂—(R_(1-aryl)), or —CH₂—(R_(1-heteroaryl)).
 97. A protected azide of formula (XII) according to claim 96 where R_(1-aryl) is phenyl.
 98. A protected azide of formula (XII) according to claim 97 where phenyl is substituted with one, two or three —F, —Cl, —Br or —I.
 99. A protected azide of formula (XII) according to claim 98 where phenyl is substituted with one or two —F.
 100. A protected azide of formula (XII) according to claim 99 where phenyl is substituted with two —F in the 3- and 5-positions giving 3,5-difluorophenyl.
 101. A protected azide of formula (XII) according to claim 95 where R₂ and R₃ are both —H.
 102. A protected azide of formula (XII) according to claim 95 where PROTECTING GROUP is t-butoxycarbonyl. (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (H) —OH, (I) —C═N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n1)—(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide , benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C═N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) is as defined below; where R_(N) is: (I) R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: (A) —CO—, (B) —SO₂—, (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are —H or C₁-C₄ alkyl, (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from the group consisting of —O—, —S— and —NR′— and where R′ and R″ are as defined above, and (E) a single bond; where R_(N-1) is selected from the group consisting of: (A) R_(N-aryl) where R_(N-aryl) is phenyl, 1-naphthyl, 2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted with one, two or three of the following substituents which can be the same or different and are: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2)—OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I, (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C]₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C]₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (B) —R_(N-heteroaryl) where R_(N-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide, tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(N-heteroaryl) group is bonded by any atom of the parent R_(N-heteroaryl) group substituted by hydrogen such that the new bond to the R_(N-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four of: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) —OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I (5) —CO—OH, (6) —C═N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH2, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j)—R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) (CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄-N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five of: —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C) R_(N-aryl)—W—R_(N-aryl), where R_(N-aryl) is defined as above, (D) R_(N-aryl)—W—R_(N-heteroaryl), where R_(N-aryl) and R_(N-heteroaryl) are as defined above, (E) R_(N-aryl)—W—R_(N-heterocycle), where R_(N-heterocycle) is defined as R_(1-heterocycle), is defined above, (F) R_(N-heteroaryl)—W—R_(N-aryl) where R_(N-aryl) and R_(n-heteroaryl) are as defined above, (G) R_(N-heteroaryl)—W—R_(N-heteroaryl), where R_(N-heteroaryl) is as defined above, (H) R_(N-heteroaryl)—W—R_(N-) _(1-heterocycle), where R_(N-1-heterocycle) is as defined as R_(1-heterocycle) is as defined above, and where R_(N-heteroaryl) is as defined above, (I) R_(N-heterocycle)—W—R_(N-aryl), where R_(N-heterocycle) is as defined as R_(1-heterocycle) is defined and where R_(N-aryl) are as defined above, (J) R_(N-heterocycle)—W—R_(N-heteroaryl), where R_(N-heterocycle) is as defined as R_(1-hetetocycle) as defined above and R_(N-heteroaryl) are as defined above, and (K) R_(N-heterocycle)—W—R_(N-1-heterocycle), where R_(N-heterocycle) and R_(N-heteroaryl) are as defined above, where W is (6) —(CH₂)₀₋₄—, (7) —O—, (8)—S(O)₀₋₂—, (9) —N(R_(N-5))— where R_(N-5) is as defined above, or (10) —CO—, (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where RNA is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, —Cl, (IV) —CO—(C₁-C₆ alkyl)-S-(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is as defined above, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, or —Cl, (V) —CO—CH(—CH₂)₀₋₂—O—R_(N-10)) —(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)) where R_(N-aryl) and R_(N-heteroaryl) are as defined above, where R_(N-10) is selected from the group consisting of: (A) —H, (B) C₁-C₆ alkyl, (C) C₃-C₇ cycloalkyl, (D) C₂-C₆ alkenyl with one double bond, (E) C₂-C₆ alkynyl with one triple bond, (F) R_(1-aryl) where R_(1-aryl) is as defined above, and (G) R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above, or (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substituted with one or two substitutents selected from the group consisting of: (A) —(CH₂)₀₋₄—OH, (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy, (C) —(CH₂)₀₋₄-C₁-C₆ thioalkoxy, (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —(CH₂)₀₋₄—CO—RN₄ where R_(N-4) is as defined above, (G) —(CH₂)₀—SO₂—(C₁-C₈ alkyl), (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl.
 124. An azide of formula (XV) according to claim 123 where R₁ is: —CH₂—(R_(1-aryl)), or —CH₂—(R_(1-heteroaryl)).
 125. An azide of formula (XV) according to claim 124 where R_(1-aryl) is phenyl.
 126. An azide of formula (X-V) according to claim 125 where phenyl is substituted with one, two or three —F, —Cl, —Br or —I.
 127. An azide of formula (X(V) according to claim 126 where phenyl is substituted with one or two —F.
 128. An azide of formula (XV) according to claim 127 where phenyl is substituted with two —F in the 3- and 5-positions giving 3,5-difluorophenyl.
 129. An azide of formula (XV) according to claim 123 where R₂ and R₃ are both —H.
 130. An azide of formula (XV) according to claim 123 where R_(N) is: R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: —CO—, and —SO₂—, where R_(N-1) is selected from the group consisting of: R_(N-aryl), and —R_(N-heteroaryl).
 131. An azide of formula (XV) according to claim 130 where R_(N) is: R_(N1)—X_(N)— where X_(N) is selected from the group consisting of: —CO—, where R_(N-1) is selected from the group consisting of: R_(N-aryl) —R_(N-heteroaryl).
 132. An azide of formula (XV) according to claim 131 where R_(N) is: (a) R_(N-1)—X_(N,)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one —CO—NR_(N-2)R_(N-3) where the substitution on phenyl is 1,3- and where R_(N-2) and R_(N-3) are the same and are C₃ alkyl, or (b) R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one Cl alkyl and with one —CO—NR_(N-2)R_(N-3) where the substitution on the phenyl is 1,3,5- and where R_(N-2) and R_(N-3) are the same and are C₃ alkyl.
 133. An azide of formula (XV) according to claim 123 which is N¹-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N³,N³-dipropylisophthalamide.
 134. A free amine of formula (XVI)

where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl); (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)—, where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, where R_(N) is: (I) R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: (A) —CO—, (B) —SO₂— (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are —H or C₁-C₄ alkyl, (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from the group consisting of —O—, —S— and —NR′— and where R′ and R″ are as defined above, and (E) a single bond; where R_(N-1) is selected from the group consisting of: (A) R_(N-aryl) where R_(N-aryl) is phenyl, 1-naphthyl, 2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted with one, two or three of the following substituents which can be the same or different and are: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2)—OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I, (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl), and (k) —R_(1-heteroaryl), (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl), (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl), (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle), (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)), (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)), (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄-N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀4—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (B)—R_(N-heteroaryl) where R_(N-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofiranyl, isobenzotetrahydrodiienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide, tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide, where the R_(N-heteroaryl) group is bonded by any atom of the parent R_(N-heteroaryl) group substituted by hydrogen such that the new bond to the R_(N-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four of: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) —OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl), and (k) —R_(1-heteroaryl), (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl), (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl), (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle), (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)), (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)), (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄-N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five of: —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C) R_(N-aryl)—W—R_(N-aryl), (D) R_(N-aryl)—W—R_(N-heteroaryl), (E) R_(N-aryl)—W—R_(N-1-heterocycle), where R_(n-1-heterocycle) is defined as R_(1-heterocycle), (F) R_(N-heteroaryl)—W—R_(N-aryl), (G) R_(N-heteroaryl)—W—R_(N-heteroaryl), (H) R_(N-heteroaryl)—W—R_(N-1-heterocycle), (I) R_(N-heterocycle)—W—R_(N-aryl), (J) R_(N-heterocycle)—W—R_(N-heteroaryl), and (K) R_(N-heterocycle)—W—R_(N-1-heterocycle), where W is (11) —(CH₂)₀₋₄—, (12) —O—, (13)—S(O)₀₋₂—, (14) —N(R_(N-5))— where R_(N-5) is as defined above, or (15) —CO—₁ (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where RN—S are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, —Cl, (IV) —CO—(C₁-C₆ alkyl)-S-(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A)—OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is as defined above, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, or —Cl, (V) —CO—CH(—CH₂)₀₋₂—O—R_(N-10))—(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)) where R_(N-aryl) and R_(N-heteroaryl) are as defined above, where R_(N-10) is selected from the group consisting of: (A) —H, (B) C₁-C₆ alkyl, (C) C₃-C₇ cycloalkyl, (D) C₂-C₆ alkenyl with one double bond, (E) C₂-C₆ alkynyl with one triple bond, (F) R_(1-aryl) where R_(1-aryl) is as defined above, and (G) R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above, or (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substituted with one or two substitutents selected from the group consisting of: (A) —(CH₂)₀₋₄—OH, (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy, (C) —(CH₂)₀₋₄-C₁-C₆ thioalkoxy, (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is as defined above, (G) —(CH₂)₀₋₄—SO₂—(C₁-C₈ alkyl), (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl, where R₁ is: —CH₂-phenyl where -phenyl is substituted with two —F, —(CH₂)_(n1)—R_(1-heteroaryl) or —(CH₂)_(n1)—R_(1-heterocycle).
 135. A free amine of formula (XVI) according to claim 134 where R₁ is: —(CH₂)_(n-1)—(R_(1-heteroaryl)).
 136. A free amine of formula (XVI) according to claim 135 where n₁ is
 1. 137. A free amine of formula (XVI) according to claim 134 where R₁ is: —(CH₂)_(n1)—(R_(1-heterocycle)).
 138. A free amine of formula (XVI) according to claim 137 where n₁ is
 1. 139. A free amine of formula (XVI) according to claim 134 where phenyl is substituted in the 3- and 5-positions giving 3,5-difluorophenyl.
 140. A free amine of formula (XVI) according to claim 134 where R₂ and R₃ are both —H.
 141. A free amine of formula (XVI) according to claim 134 where R_(N) is: R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: —CO—, and —SO₂—, where R_(N-1) is selected from the group consisting of: R_(N-aryl), and —R_(N-heteroaryl).
 142. A free amine of formula (XVI) according to claim 141 where R_(N) is: R_(N-1)—X_(N)— where X_(N) is: —CO—, where R_(N-1) is selected from the group consisting of: R_(N-aryl), and —R_(N-heteroaryl).
 143. A free amine of formula (XVI) according to claim 142 where R_(N) is: (a) R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one —CO—NR_(N-2)R_(N-3) where the substitution on phenyl is 1,3- and where R_(N-2) and R_(N-3) are the same and are C₃ alkyl, or (b) R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one Cl alkyl and with one —CO—NR_(N-2)R_(N-3) where the substitution on the phenyl is 1,3,5- and where R_(N-2) and R_(N-3) are the same and are C₃ alkyl.
 144. A free amine of formula (XVI) according to claim 134 which is N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide.
 145. A method of treating a patient who has, or in preventing a patient from getting, a disease or condition selected from the group consisting of Alzheimer's disease, for helping prevent or delay the onset of Alzheimer's disease, for treating patients with mild cognitive impairment (MCI) and preventing or delaying the onset of Alzheimer's disease in those who would progress from MCI to AD, for treating Down's syndrome, for treating humans who have Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treating cerebral amyloid angiopathy and preventing its potential consequences, i.e. single and recurrent lobar hemorrhages, for treating other degenerative dementias, including dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease and who is in need of such treatment which comprises administration of a therapeutically effective amount of a compound selected from the group consisting of a substituted amine of formula (X)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n-1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (H) —OH, (I) —C≡N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n1)—(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isocbromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)-, where R_(N-2) is as defined below; where R_(N) is: (I) R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: (A) —CO—, (B) —SO₂— (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are —H or C₁-C₄ alkyl, (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from the group consisting of —O—, —S— and —NR′— and where R′ and R″ are as defined above, and (E) a single bond; where R_(N-1) is selected from the group consisting of: (A) R_(N-aryl) where R_(N-aryl) is phenyl, 1-naphthyl, 2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted with one, two or three of the following substituents which can be the same or different and are: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) —OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I, (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (B)—R_(N-heteroaryl) where R_(N-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofaranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide, tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(N-heteroaryl) group is bonded by any atom of the parent R_(N-heteroaryl) group substituted by hydrogen such that the new bond to the R_(N-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four of: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2)—OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂₋(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five of: —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C) R_(N-aryl)—W—R_(N-aryl), where R_(N-aryl) is defined as above, (D) R_(N-aryl)—W—R_(N-heteroaryl), where R_(N-aryl) and R_(N-heteroaryl) are as defined above, (E) R_(Naryl)—W—R_(N-1-hetercycle), where R_(N-heterocycle) is defined as R_(1-heterocycle), is defined above, (F) R_(N-heteroaryl)—W—R_(N-aryl), where R_(N-aryl) and R_(n-heteroaryl) are as defined above, (G) R_(N-heteroaryl)—W—R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above, (H) R_(N-heteroaryl)—W—R_(N-1-heterocycle), where R_(N-1-heterocycle) is as defined as R_(1-heterocycle) is as defined above, and where R_(N-heteroaryl) is as defined above, (I) R_(N-heterocycle)—W—R_(N-aryl), where R_(N-heterocycle) is as defined as R₁ heterocycle is defined and where R_(N-aryl) are as defined above, (J) R_(N-heterocycle)—W—R_(N-heteroaryl), where R_(N-heterocycle) is as defined as R_(1-heterocycle) as defined above and R_(N-heteroaryl) are as defined above, and (K) R_(N-heterocycle)—W—R_(N-1-heterocycle), where R_(N-heterocycle) and R_(N-heteroaryl) are as defined above, where W is (16) —(CH₂)₀₋₄—, (17) —O—, (18)—S(O)₀₋₂—, (19)-N(R_(N-5))- where R_(N-5) is as defined above, or (20) —CO—, (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl isoptionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -ø, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8)s are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, —Cl, (IV) —CO—(C₁-C₆ alkyl)—S—(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A)—OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is as defined above, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, or —Cl, (V) —CO—CH(—CH₂)₀₋₂—O—R_(N-10))—(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)), where R_(N-10) is selected from the group consisting of: (A) —H, (B) C₁-C₆ alkyl, (C) C₃-C₇ cycloalkyl, (D) C₂-C₆ alkenyl with one double bond, (E) C₂-C₆ alkynyl with one triple bond, (F) R_(1-aryl), and (G) R_(N-heteroaryl), or (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substituted with one or two substitutents selected from the group consisting of: (A) —(CH₂)₀₋₄—OH, (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy, (C) —(CH₂)₀₋₄-C₁-C₆ thioalkoxy, (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is as defined above, (G) —(CH₂)₀₋₄—SO₂—(C₁-C₈ alkyl), (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl, where R_(C) is: (I) —C₁-C₁₀ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) where R_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO—O—(C₁-C₄ alkyl), and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y) are —H, C₁-C₄ alkyl optionally substituted with one or two —OH, C₁-C₄ alkoxy optionally substituted with one, two, or three of: —F, —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, C₂-C₆ alkenyl containing one or two double bonds, C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-, and where R_(C-x) and R_(C-y) are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)— and R_(C-aryl) is the same as R_(N-aryl); (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) where R_(C-heteroaryl) is the same as R_(N-heteroaryl) and R_(C-x) and R_(C-y) are as defined above, (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where R_(C-aryl), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) where R_(C-heteroaryl) R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl) where R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, and R_(C-heterocycle) is the same as R_(N-heterocycle), (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle) where R_(C-heteroaryl), R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) where R_(C-heterocycle), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl) where R_(C-heterocycle), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle) where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XV) —[C(R_(C-1))(R_(C-2))_(1-3 —CO—N—(R) _(C-3))₂ where R_(C-1) and R_(C-2) are the same or different and are selected from the group consisting of: (A) —H, (B) —C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)1 ₂—S(O)₀₋₂—(C₁-C₆ alkyl), (F) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (G) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as defined for R_(1-aryl), (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (I) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (J) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (K) —R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—, —S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, and where R_(C-aryl) is as defined above, (N) —(CH₂)₁-4—R_(C-4)-CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) and R_(C-heteroaryl) are as defined above, and (O) —R_(C′-aryl) where R_(C′-aryl) is as defined above, and where R_(C-3) is the same or different and is: (A) —H, (B) —C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, 4,—OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (F) —R_(C′-aryl) where R_(C′-aryl) is as defined above, (G) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (H) —R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (I) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as defined above, (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, or (K) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or different and are as defined above, (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the same or different and are as defined above, (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)) where R_(C-aryl) and R_(C-heteroaryl) are as defined above, (XIX)-cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) are as defined above where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR_(N-5), O, or S(═O)₀₋₂, and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two -C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, =O, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XX) C₂-C₁o alkenyl containing one or two double bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) C₂-C₁₀ alkynyl containing one or two triple bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁-R_(C-aryl) where R_(C-aryl) is as defined above and R_(C-6) is —(CH₂)₀₋₆—OH, (XXII) —(CH₂)₀₋₁—CHR_(C-6)-CH₂)₀₋₁—R_(C-heteroaryl) where R_(C-heteroaryl) and R_(C-6) is as defined above, (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl)) —CO—O(C₁-C₄ alkyl) where R_(C-aryl) and R_(C-heteroaryl) are as defined above, (XXIV) —CH(—CH₂—OH) —CH(—OH)-phenyl-NO₂, (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH, (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂, (XXVIII) —H, or (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) and R_(1-b) are as defined above; or a pharmaceutically acceptable salt thereof.
 146. A method of treatment according to claim 145, wherein the disease is Alzheimer's disease.
 147. A method of treatment according to claim 145, wherein the method is helping prevent or delay the onset of Alzheimer's disease.
 148. A method of treatment according to claim 145, wherein the disease is mild cognitive impairment.
 149. A method of treatment according to claim 145, wherein the disease is Down's syndrome.
 150. A method of treatment according to claim 145, wherein the disease is Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type.
 151. A method of treatment according to claim 145, wherein the disease is cerebral amyloid angiopathy.
 152. A method of treatment according to claim 145, wherein the disease is degenerative dementias.
 153. A method of treatment according to claim 145, wherein the disease is diffuse Lewy body type of Alzheimer's disease.
 154. A method of treatment according to claim 145, wherein the method is treating an existing disease.
 155. A method of treatment according to claim 145, wherein the method is preventing a disease from developing.
 156. A method of treatment according to claim 145, wherein the therapeutically effective amount for oral administration is from about 0.1 mg/day to about 1,000 mg/day; for parenteral, sublingual, intranasal, intrathecal administration is from about 0.5 to about 100 mg/day; for depo administration and implants is from about 0.5 mg/day to about 50 mg/day; for topical administration is from about 0.5 mg/day to about 200 mg/day; for rectal administration is from about 0.5 mg to about 500 mg.
 157. A method of treatment according to claim 156, wherein the therapeutically effective amount for oral administration is from about 1 mg/day to about 100 mg/day and for parenteral administration is from about 5 to about 50 mg daily.
 158. A method of treatment according to claim 157 where the therapeutically effective amount for oral administration is from about 5 mg/day to about 50 mg/day.
 159. A method of treatment according to claim 145 where: where R₁ is: —(CH₂)₀₋₁—(R_(1-aryl)), or —(CH₂)_(n1)—(R_(1-heteroaryl)) where R_(N) is: R_(N-1)—X_(N,)— where X_(N) is selected from the group consisting of: —CO—, and —SO₂—, where R_(N-1) is selected from the group consisting of: —R_(N-aryl), and —R_(N-heteroaryl), —CO—CH(—CH₂)₀₋₂—O—R_(N-10))—(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroaryl)), and where R_(C) is: —C₁-C₈ alkyl, —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl or -cyclohexyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 160. A method of treatment according to claim 159 where: where R₁ is: —(CH₂)—(R_(1-aryl)), or —(CH₂)—(R_(1-heteroaryl)); where R₂ is —H; where R₃ is —H; where R_(N) is: R_(N-1)—X_(N)— where X_(N) is: —CO—, where R_(N-1) is selected from the group consisting of: —R_(N-aryl), and —R_(N-heteroaryl), where R_(C) is: —(CH₂)₀₋₃—(C₃-C₇) cycloalkyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle), or -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 161. A method of treatment according to claim 160 where R_(C) is: —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl), —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), or -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 162. A method of treatment according to claim 145 where R₁ is: —(CH₂)—(R_(1-aryl)) where R_(1-aryl) is phenyl.
 163. A method of treatment according to claim 162 where R₁ is: —(CH₂)—(R_(1-aryl)) where R_(1-aryl) is phenyl substituted with two —F.
 164. A method of treatment according to claim 163 where the —F substitution is 3,5-difluorobenzyl.
 165. A method of treatment according to claim 145 where R₂ is —H.
 166. A method of treatment according to claim 145 where R₃ is —H.
 167. A method of treatment according to claim 145 where R_(N) is R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one —CO—NR_(N-2)R_(N-3) where the substitution on phenyl is 1,3-.
 168. A method of treatment according to claim 167 where R_(N-2) and R_(N-3) are the same and are C₃ alkyl.
 169. A method of treatment according to claim 145 where R_(N) is R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-aryl) where R_(N-aryl) is phenyl substituted with one C₁ alkyl and with one —CO—NR_(N-2)R_(N-3) where the substitution on the phenyl is 1,3,5-.
 170. A method of treatment according to claim 169 where R_(N-2) and R_(N-3) are the same and are C₃ alkyl.
 171. A method of treatment according to claim 145 where R_(N) is R_(N-1)—X_(N)— where X_(N) is —CO—, where R_(N-1) is R_(N-heteroaryl) where R_(N-heteroaryl) is substituted with one —CO—NR_(N-2)R_(N-3).
 172. A method of treatment according to claim 171 where R_(N-2) and R_(N-3) are the same and are —C₃ alkyl.
 173. A method of treatment according to claim 145 where R_(C) is: —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-aryl) is phenyl, —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl), or -cyclopentyl or -cyclohexyl ring fused to a R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle).
 174. A method of treatment according to claim 173 where R_(C) is: —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-aryl) is phenyl.
 175. A method of treatment according to claim 174 where phenyl is substituted in the 3-position or 3,5-positions.
 176. A method of treatment according to claim 173 where R_(C) is: —(CH₂)—R_(C-heteroaryl).
 177. A method of treatment according to claim 173 where R_(C) is: —(CH₂)—R_(C-heterocycle).
 178. A method of treatment according to claim 173 where R_(C) is: -cyclohexyl ring fused to a phenyl ring.
 179. A method of treatment according to claim 145 where the pharmaceutically acceptable salt is selected from the group consisting of salts of the following acids acetic, aspartic, benzenesulfonic, benzoic, bicarbonic, bisulfuric, bitartaric, butyric, calcium edetate, camsylic, carbonic, chlorobenzoic, citric, edetic, edisylic, estolic, esyl, esylic, formic, fumaric, gluceptic, gluconic, glutamic, glycollylarsanilic, hexamic, hexylresorcinoic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxynaphthoic, isethionic, lactic, lactobionic, maleic, malic, malonic, mandelic, methanesulfonic, methylnitric, methylsulfuric, mucic, muconic, napsylic, nitric, oxalic, p-nitromethanesulfonic, pamoic, pantothenic, phosphoric, monohydrogen phosphoric, dihydrogen phosphoric, phthalic, polygalactouronic, propionic, salicylic, stearic, succinic, succinic, sulfamic, sulfanilic, sulfonic, sulfuric, tannic, tartaric, teoclic and toluenesulfonic.
 180. A method of treatment according to claim 145 where the substituted amine (X) is selected from the group consisting of: N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(ethylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(benzylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isopropylamino)propyl]-N³, N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(4-toluidino)propyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methoxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, ethyl {[(3S)-3-({3-[(dipropylamino)carbonyl]benzoyl}amino)-2-hydroxy-4-phenylbutyl]amino}(phenyl)acetate, N¹-((1S)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-chlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(4-chlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-hydroxyethoxy)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-1-ylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(tetrahydro-2-furanylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,2-diethoxyethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(butylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(cyclohexylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(2-aminobenzyl)amino]-1-benzyl-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-pyridinylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-pyrrolidinyl)ethyl]amino}propyl)-N³N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-butoxypropyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-isopropoxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propyl]-N³,N³ dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-phenylpropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{((S,2R)-1-benzyl-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-N³,N¹-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,3-dimethylbutyl)amino]-2-hydroxypropyl}-N³N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-phenylbutyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(4-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-chlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(4-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-pyridinyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-pyridinylmethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(1-methyl-2-pyrrolidinyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,3-dimethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-chloro-6-phenoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,3-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[4-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-({2-[4-(aminosulfonyl)phenyl]ethyl}amino)-1-benzyl-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-methylbellzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3,4,5-trimethoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,4-dimethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-1-(1-naphthyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-1-(1-naphthyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxy-3-methoxybenzyl)amino]propyl}-N³,N3-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dihydroxybenzyl)amino]-2-hydroxypropyl}-N³ N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-methylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-methylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(2-propynylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(2-fluorophenyl)ethyl]amino-3-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(3-fluorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(4-fluorophenyl)ethyl] amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(4-bromophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S)-1-benzyl-2-hydroxy-3-{[2-(3-methoxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(2,4-dichlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(3-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S)-1-benzyl-3-{[2-(2,5-dimethoxyphenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-methylphenyl)ethyl]amino}propyl)-N¹,N¹-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[(1R)-1-benzyl-2-hydroxyethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-morpholinyl)propyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(4-morpholinyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-hydroxybutyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-thienyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxybutyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S)-2-hydroxy-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,4-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R)-2-hydroxy-1-phenylethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(4-tert-butylbenzyl)amino]-2-hydroxypropyl}-N³,N³- dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-N³,N³- dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1,1-dimethyl-2-oxoethyl]aminopropyl)-5-methyl-N³, N3-dipropylisophthialamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]propyl3 amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(ethylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isobutylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isobutylamino)-2-methyl-3-oxopropyl]amino,propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[4-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-benzyl-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[2-(dimethylamino)ethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(i S)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]butyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-2-(benzylamino)-1-methyl-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-1-phenylpropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1S)-2-(ethylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-2-oxo-1-phenylethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclohexylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N I -[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N.—I{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-2-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3R,5S)-3,5-dimethoxycyclohexyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, dimethyl (1R,3S)-5-{[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]aminol}-1,3-cyclohexanedicarboxylate, (1R,3S)-5-{[(2R,3S)4-(3,5-difluorophenyl)-3-(13-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3cyclohexanedicarboxylic acid, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-1-phenylpropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-chlorobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(2-propylpentyl)sulfonyllbenzamide, N¹-[((S,2R)-3-[([1,I ′-biphenyl]-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹- ((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylpropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-thienylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyrazinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-difluorobenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(1,3-benzodioxol-5-ylmethyl)amino]-1-benzyl-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-” (trifluoromethoxy)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1,2,3,4-tetrahydro-1-naphthalenylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methoxy-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-chloro-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-fluoro-N³,N³-dipropylisophthalamide, N²-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N5,N⁵-dipropyl-2,5-thiophenedicarboxamide, N⁴-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N²,N²-dipropyl-2,4-pyridinedicarboxamide, N⁴-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁶,N6dipropyl-4,6- pyrimidinedicarboxamide, N-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-(4-morpholinylcarbonyl)benzamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N¹-[(1S,2R)-3-{[(1R)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N3N3-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(pentylamino)propyl]-N³,N³-dipropylisophthalamide, N¹-[(1S)-3-({2-[4-(aminosulfonyl)phenyl]ethyl}amino)-1-benzyl-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, 3-benzoyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}[1,1′-biphenyl]-3-carboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-(2-methoxyethyl)-N3-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-ethoxybenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-naphthamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1R)-1,2,3,4-tetrahydro-1-naphthalenylaminopropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1R)-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-fluoro-5-(trifluoromethyl)benzyl]amino}-2-,hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,3-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-4-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2,5-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-difluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-fluoro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(2,3-dihydro-1H-inden-2-ylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-benzyl-2-hydroxy-3-[(3-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-(difluoromethoxy)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³′-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(5-methyl-2-pyrazinyl)methyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-bromo-4-fluorobenzyl)amino]-2-hydroxypropyl}-N³N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethylbenzyl)amino]-2-hydroxypropyl3-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isobutoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, -. 1-N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-methyl-1,3-thiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-methyl-N³-propylisophthalamide, N²-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-Ns,N⁵-dipropyl-2,5-fiurandicarboxamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(l -methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1,2-diphenylethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, isomer A, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, isomer B, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(dimethylamino)benzamide, N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl3-2-methyl-i H-benzimidazole-5-carboxamide, 3-(aminosulfonyl)-N-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-chlorobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-cyanobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-chloro-3-nitrobenzamide, methyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-nitrobenzoate, tert-butyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]phenylcarbamate, N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl]-9,10-dioxo-9, 1 0-dihydro-2-anthrancenylcarboxamide, N-[(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1H-1,2,3-benzotriazole-6-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-(3-methyl-5-oxo4,5-dihydro-1H-pyrazol-1-yl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1H-indole-5-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-fluoro-5-(trifluoromethyl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(trifluoromethyl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl 34-(butylamino)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(trifluoromethoxy)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-dimethoxybenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-dimethylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-difluorobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,5-dichlorobenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-4-(benzyloxy)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1,3-benzodioxole-5-carboxamide, 3-(acetylamino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide, 4-(acetylamino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}benzamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3,5-dimethyl4-isoxazolyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-phenylpropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-firylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-3-furanylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-propoxybenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-hydroxy-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-methyl-1-(3-methylphenyl)ethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1S)-l ,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2,5-dimethylbenzyl)amino-3-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-5-methylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(1-benzofuran-2-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1R)-1-(3-bromophenyl)ethyl]amino}-1-(3,5-difluorobenzyl)-²-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyl(butyryl)amino]-5-methylbenzamide, N¹-f ¹-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino{propyl}-4-methyl-N³,N³-dipropylisophthalamide, N³-{1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-methyl-N¹,N¹-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-butyl-1H-indole-6-carboxamide, N¹-[(1S,2R)-3-anilino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, 5-bromo-N ′-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methylpentanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methylpentanamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-hydroxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-²-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³,N³-dipropylisophthalamide hydrochloride, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, I -N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide trifluroacetate, 5-(aminosulfonyl)-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-pyrrolidinylsulfonyl)isophthalamide, N^(l)-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl-5-[(dimethylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-methyl-3-(methylsulfonyl)propanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)arnino]propyl)-3-(methylsulfonyl)propanamide, 2-amino-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyll}-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)anino]propyl}-5-(methylsulfonyl)pentanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenrzy)amino]propyl}-N⁴-phenylsuccinamide, (3R)-N⁴-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2,2,3-trimethylbutanediamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N¹-dipropylpentanediamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-oxo-4-(1-piperidinyl)butanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-metioxybenzyl)amino]propyl}-N⁴,N⁴-dipropylsuccinamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵-phenylpentanediamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3,3-dimethyl-4-oxo-4-(1-piperidinyl)butanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-(isopentylsulfonyl)butanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2,2-dimethyl-N4,N⁴-dipropylsuccinamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-[(dipropylamino)sulfonyl]butanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-[(methylanilino)sulfonyl]butanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(methylanilino)sulfonyl]propanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}acetamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(isopentylsulfonyl)propanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide and N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-isobutyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-tert-butyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dimethyl-N⁵,N5-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-amino-1-benzyl-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-1-benzyl-2-hydroxy-3-(isopentylamino)propyl]-N³,N³-dipropy1 1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³-propyl-1,3,5-benzenetricarboxamide, N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyry1(propyl)amino]-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-aminobenzyl)amino]-1-(3,5-difluorobenzy1)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}octanamide, N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-methylbenzamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1H-isoindol-3-ylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹- ((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S,5R)-2-isopropyl-5-.—methylcyclobexyl]amino}propyl)-5-methyl-N3,N¹-dipropylisophthalamide, N¹,N¹-diallyl-5-chloro-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}isophthalamide, N¹,N¹-diallyl-5-chloro-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}isophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)aminol-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4,5-dimethyl-2-furyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(cyclopropylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-2-filranylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-oxo-3-azepanyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-methyl-2-furyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-di(2-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropenylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(hexylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}4-(3-methyl-5-oxo4,5-dihydro-1H-pyrazol-1-yl)benzamide, methyl 4-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)benzoate, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-isoxazolylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, (1R,2R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-fUranylmethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, 4-(butyrylamino)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}benzamide, N¹-[(1S,2R)-3-[(3-amino-3-oxopropyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N3-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-Ns⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide I-oxide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N— -{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-oxabicyclo[2.2. 1]hept-2-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)aminoJ-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-methyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-²-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3R)-2-oxoazepanyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclobutylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(5-hexynylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-N⁵,N5-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(2-furyl)-1-methylethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyleaminopropyl)-5-methyl-N3N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide, N 1-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-(2-chlorophenyl)ethyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(2-oxo-1-pyrrolidinyl)propyl]amino}propyl)-N ,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(cyclohexylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(cyclopropylarnino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(2-oxo-3-azepanyl)amino]propyl}-N³,N³-dipropylisophthalamide, N-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-(butylsulfonyl)benzamide, N¹-[(1S,2R)-1-benzyl-3-({2-[(2-ethylhexyl)oxy]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1 yl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[1-(4-hydroxyphenyl)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-benzyl-3-(cycloheptylamino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[([1, I′-biphenyl]-2-ylnethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(2-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(dimethylamino)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-naphthamide, N¹-[(1S,2R)-1-benzyl-3-({2-[({5-[(dimethylamino)methyl]-2-furyl}methyl)sulfanyl]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N ′-[(1S,2R)-1-benzyl-3-({2-[(2-chloro-6-fluorobenzyl)sulfanyl]ethyl}amino)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[([1, I′-biphenyl]-4-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1-naphthylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-imidazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-phenyl-1H-imidazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl- lH-imidazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl-4-chloro-1H-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(6-chloroimidazo[2, 1-b] [1,3]thiazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N 3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-benzimidazol-2-yl)methyl]aminopropyl)-5-methyl-N³, N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-hydroxy-1-naphthyl)methyl]amino}propyl)-5-methyl-N³, N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-oxo4H-chromen-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol4-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-({[5-cyano-6-(methylsulfanyl)-2-pyridinyl]methyl}amino)-1-(3,,5-difluorobenzyl)-2-hydroxypropyl]-5-metliyl-N ,N3-dipropylisophthalamide, [5-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-2-furyl]methyl acetate, N ′-[(1S,2R)-3-[(i -benzofiuran-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, 5 methyl 4-({[(2R,3S)-4-(3,5-difluorophenyl)-3-(f 3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutylJamino}methyl)-1-methyl-i H-pyrrole-2-carboxylate, N¹-[(1S,2R)- i -(3,5-difluorobenzyl)-2-hydroxy-3-({[1-(phenylsulfonyl)-1H-pyrrol-2-ylmethyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, 10 N¹-((1 $,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(l1-methyl-i H-pyrrol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(4-chloro-1-methyl-1H-pyrazol-3-yl)methyl]amino}-1-(3,5-difluorobenzyD)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3,5-dimethyl-1-phenyl-1H-pyrazol-1 5 4-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(5-chloro-3-methyl-1-phenyl-1H-pyrazol4-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-phenyl-1H-pyrazol-4-20 yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(Schloro-2-thienyl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-phenoxy-2-thienyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 25 N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-quinolinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-quinolinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(I-methyl-i H-indol-2-30 yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1-benzyl-1H-indol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(i -methyl-i H-indol-3-yl)methyljamino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[({1-[(4-methylphenyl)sulfonyl]-1H-indol-3-yl}methyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl-1 lH-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, methyl 3-({[(2R,3S)4-(3,5-difluorophenyl)-3-(f{3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)- H-indole-6-carboxylate, 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-amino)carbonyl]-5-[butyl(butyryl)amino]benzyl diethyl phosphate, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(cyanomethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(hydroxymethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobe)amino]propyl -N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3(trifluoromethyl)benlzylamino}propyl)-5-ethynlyl N³N³-dipropylisophthalamide N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]-5-ethynyl-N¹,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(8-quinolinyl)isophthalamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-4′-methoxy-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(3-thienyl)isophthalamide, N-{(1R,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide, N¹-(4-hydroxybutyl)-N³-{(1S)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N 1-propylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³-(3-hydroxypropyl)-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(4-methylphenyl)propyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl -1,3-dioxo-2-propyl-5-isoindolinecarboxamide, N-{(1R,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-bromo-5-methylbenzamide, 3-bromo-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-N¹,N¹-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-(2-furyl)-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3′,5,5 ′-trimethyl-1, I′-biphenyl-3-carboxamide, 3′-Acetyl-N-{(1S,2R)-1-benzy1-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl[1,1′-biphenyl]-3-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3 ′-methoxy-5-methyl[1,1′-biphenyl]-3-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl[1,1′-biphenyl]-3-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl)-3-methyl-5-(2-thienyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl) amino]propyl}-3-methyl-5-(3-thienyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino] propyl}-3-methyl-5-(3-thienyl)benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}A4-methyl-3-(3-thienyl)benzamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³,N⁵,N⁵-tetrapropylbenzene-1,3,5-tricarboxamide, N¹-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide, Ethyl 3-[({(1S,2R)-1-benzr1-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoate, N¹-{(1S,2R)-2-Hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 5-Amino-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(trifluoroacetyl)amino]isophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl)-N³,N³-dipropyl-5-[(thien-2-ylcarbonyl)amino]isophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl3-5-(methacryloylamino)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(2,2-dimethylpropanoyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide. N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methylthio)pentanamide, tert-butyl (2R,3S)-3-({3-[(dipropylamino)sulfonyll- propanoyl}amino)-2-hydroxy4-phenylbutyl(3-methoxybenzyl)carbamate N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-[propionyl(propyl)amino]benzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-butyl-1H-indole-5-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-bromo-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyl(propionyl)amino]-5-methylbenzamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-methyl-1-propyl-1H-indole-6-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-(1-propylbutyl)-1H-indole-6-carboxamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{1[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoic acid, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-(dipropylamino)isonicotinamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-hydroxy-2-(4-methylphenyl)acetamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxy-N3-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-hydroxy-2-(4-methoxy-3-nitrophenyl)acetamide, 5-(aminosulfonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-methoxybenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]-4-hydroxy-3-(pyrrolidin-1-ylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(3,5-dimethylisoxazol4-yl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide, 3-(cyclohexylcarbonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³-propylisophthalamide, 3-[cyclohexyl(hydroxy)methyl]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino-3-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N³,N³-dipropylisophthalamide N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-oxadiazol -5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropy I}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-hydroxybut-1-ynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 1-{3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropy l}amino)carbonyl]-5-methylbenzoyl}-L-prolinamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-isopropyl-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-prop-2-ynylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyll}-N³isobutyl-5-methylisophthalamide, N¹-(sec-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,51 ifluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diethyl-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-isopropyl-N³,5-dimethylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N′,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isobutyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N3-isopropyl-5-methylisophthalamide, N¹,N¹-diallyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, 3-(azepan-1-ylcarbonyl)-N-{(1S,2R)-1-(3,5-difluorobenzy1)-3-[(3-ethylbenzyl)am ino]-2-hydroxypropyl}-5-methylbenzamide N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diisopropyl-5-methylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyil}-N¹-ethyl-5-methylisophthalamide, N¹-(cyclopropylmethyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N¹-propylisophthalamide, 1-{3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropy l}amino)carbonyl]-5-methylbenzoyl}-D-prolinamide, N¹-cyclohexyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N′,5-dimethylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-{[1-(3-methylphenyl)cycloprop yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(1,2,3,4-tetrahydronaphthalen-1-ylamino)propyl]-N⁵,N5-diisopropylpyridine-3,5-dicarboxamide, and N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide.
 181. A method of treatment according to claim 180 where the substituted amine (X) is selected from the group consisfing of: N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2-furylmethyl)amino]-2-hydroxypropyl3-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(2-hydroxyethoxy)ethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(2-aminobenzyl)amino]-1-benzyl-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[2-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,5-dimethoxybenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dichlorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N³,N³-dipropylisophthalamide, N^(l)-{(1S)-1-benzyl-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-5-methyl-N3N3-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-1,1-dimethyl-2-oxoethyl]amino}propyl)-5-methyl-N3 N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1R)-1-[(isobutylamino)carbonyl]propyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isobutylamino)-2-methyl-3-oxopropyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-benzyl-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]-2-methylpropyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1S)-1-[(benzyloxy)methyl]-2-(isobutylamino)-2-oxoethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophithalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N I-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({(1S)-1-[(isobutylamino)carbonyl]butyl}amino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3- ([(1S)-1-(hydroxymethyl)-2-(isobutylamino)-2-oxoethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamnide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(cyclohexylamino)-1-(3,5-difluorobenzy1)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzy1)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxypropyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, (1R,3S)-5-{[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}-1,3-cyclohexanedicarboxylic acid, N¹-[(1S,2R)-3-[([1,1′-biphenyl]-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-⁵-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenylpropyl)amino]propyl}-⁵-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-thienylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyrazinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimetlioxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N3 N3-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethoxy)benzyl]aminopropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-fluorobenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropoxybenzyl)amino]propyl -5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-bromobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methoxy-N³,N³-dipropylisophthalamide N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-chloro-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-fluoro-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1,3-thiazol-5-ylmethyl)amino]propyl}-N5,N⁵-dipropyl-3,5-pyridinedicarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}[1,1′-biphenyl]-3-carboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-(2-methoxyethyl)-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1R)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(l R)-3-{[3,5-bis(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[2-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-fluoro-5-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-fluoro-3-(trifluoromethyl)benzyl]amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[4-chloro-3-(trifluoromethyl)benzyljamino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N-{(1S)-1-benzyl-2-hydroxy-3-[(3-nitrobenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-3-{[3-(difluoromethoxy)benzyl] amino}-2-hydroxypropyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethoxybenzyl)amino-3-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-bromo-4-fluorobenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethoxybenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-phenoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-methyl-1,3-thiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³-methyl-N³-propylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-Ns,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, isomer B, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-furylmethyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(tetrahydro-3-furanylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-propoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-pyridinylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-hydroxy-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-methyl-1-(3-methylphenyl)ethyl]amino}propyl)-5-methyl-N3N3-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1S)-1,2,3,4-tetrahydro-1-naphthalenylamino]propyl}-5-melhyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(2,5-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[2-chloro-5-(trifluoromethyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-hydroxy-5-methylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1R)-1-(3-bromophenyl)ethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-hydroxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-cyano-N³,N³-dipropylisophthalamide hydrochloride, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 5-(aminosulfonyl)-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N-dipropylisophthalamide, *N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1-pyrrolidinylsulfonyl)isophthalamide, N¹-{(S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl-5-[(methylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(dimethylamino)sulfonyl]-N³,N³-dipropylisophthalamide, N— t(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-oxo-5-(1-piperidinyl)pentanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-tert-butyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybeizyl)amino]propyl}-5-cyano-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-1-propyl-1H-indole-6-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3,4-dimethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-aminobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}amino)propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(1R)-2,3-dihydro-1H-inden-1-ylamino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, 5-chloro-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N³,N³-bis(2-methoxyethyl)isophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino}propyl]-N¹,N¹-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4,5-dimethyl-2-furyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthaamide, N¹- I S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopentyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N ′-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropenylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-propoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(hexylamino)-2-hydroxypropyl]-5-nmethyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzamide, methyl 4-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)benzoate, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxyethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(5-isoxazolylmethyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, (1R,2R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N ,N2-dipropyl-1,2-cyclopropanedicarboxamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2S)-tetrahydro-2-furanylmethyl]amino}propyl)-N¹,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(2-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N³-[(1S,2R)-3-(benzylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide I-oxide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(7-oxabicyclo[2.2. 1 ]hept-2-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-methyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(butylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-(5-hexynylamino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-methyl-2-furyl)methyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-methyl-1-phenylethyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3- t [1-(2-furyl)-1-methylethyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-isoxazolyl)methyl]aminopropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(dipropylamino)sulfonyl]propanamide, N¹-[(1S,2R)-3-[([1,1′-biphenyl]4-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-imidazol-5-ylmethyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-phenyl-1H-imidazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl-4-chloro- lH-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N ′-[(1S,2R)-3-([5-cyano-6-(methylsulfanyl)-2-pyridinyl]methyl}amino)-1-(33,5-dfluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, [5-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-2-furyl]methyl acetate, N¹-[(1S,2R)-3-[(1-benzofuran-3-ylmethyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N ₃N³-dipropylisophthalamide, methyl 4-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1-methyl-i H-pyrrole-2-carboxylate, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-pyrrol-2-yl)methyl]amino}propyl)-5-methyl-N¹,N¹-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(5-chloro-2-thienyl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzl)-2-hydroxy-3-{[(1-methyl-i H-indol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(1-benzyl-1H-indol-3-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1-methyl-1H-indol-3-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[(2-butyl- H-imidazol-5-yl)methyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, methyl 3-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)-1H-indole-6-carboxylate, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-5-(cyanomethyl)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(hydroxymethyl)-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-ethynyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³,N³ dipropyl-5-prop-1-ynylisophthalamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-methoxy-N⁵,N⁵-dipropyll 1, l′-biphenyl]-3,5-dicarboxamide hydrochloride, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl -N⁵,N⁵-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-[(dimethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide, N³-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4′-[(diniethylamino)sulfonyl]-N⁵,N⁵-dipropyl-1,1′-biphenyl-3,5-dicarboxamide, N-{(1R,2R)-1-(3,5difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³-(3-hydroxypropyl)-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-ben 1-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}4-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-3enzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³,N⁵,N⁵-tetrapropylbenzene-1,3,5-tricarboxamide, N¹-{(1S,2R)-1-(3,5-Difluorobenl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropylbenzene-1,3,5-tricarboxamide, ethyl 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoate, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 5-amino-N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-[(thien-2-ylcarbonyl)amino]isophthalamide, N¹-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methacryloylamino)-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(methylthio)pentanamide, 3-amino-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-methylbutanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-ethylhexanamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(isobutylsulfonyl)amino]propanamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³-(isobutylsulfonyl)-beta-alaninamide, 5-bromo-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]-N³,N³-dipropylisophthalamide, and N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, 3-[({(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}amino)carbonyl]-5-[(dipropylamino)carbonyl]benzoic acid, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-prop-1-ynylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]pro pyl}-4-hydroxy-3-(pyrrolidin-1-ylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]pro pyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³-propylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-oxadiazol -5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropy I}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropylpyridine-3,5-dicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-hydroxybut-1-ynyl)benzyl]amino}propyl)-5-methyl-N³ N³-dipropylisophthalamide, 1-{3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropy I}amino)carbonyl]-5-methylbenzoyl}-L-prolinamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isopropyl-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-prop-2-ynylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-isobutyl-5-methylisophthalamide, N¹-(sec-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-butyl-N³-{1(S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diethyl-5-methylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,5-dimethyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isopropyl-N³,5-dimethylisophthalamide, N-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N′,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-isobutyl-N³,5-dimethylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-5-methyl-N³-propylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-N³-isopropyl-5-methylisophthalamide, N¹,N¹-diallyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, 3-(azepan-1-ylcarbonyl)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)aminol-2-hydroxypropyl}-5-methylbenzamide N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)aminoj-2-hydroxypropyl}-3-[(4-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-hydroxypiperidin-1-yl)carbonyl]-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-diisopropyl-5-methylisophthalamide, N¹-butyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N¹-ethyl-5-methylisophthalamide, N¹-(cyclopropylmethyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N¹-propylisophthalamide, N¹-cyclohexyl-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N′,5-dimethylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[1-(3-methylphenyl)cycloprop yl]amino}propyl)-5-methyl-N³,N3-dipropylisophthalamide, and N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide.
 182. A method of treatment according to claim 145 where the substituted amine (X) is selected from the group consisting of: N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylpentanoyl)-5-methylbenzamide, N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-benzyl-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylbutanoyl)-5-methylbenzamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(2-propylpentanoyl)isophthalamide, N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(2-ethylpentanoyl)-5-methylbenzamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(2-propylpentanoyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-(2-propylpentanoyl)isophthalamide, N-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propyl]-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-(2-propylpentanoyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl 3-3-methyl-5-(2-propylpentanoyl)benzamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-pyridinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-pyridinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(l -propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-(1-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-(2-propynyl)isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-(2-propynyl)isophthalamide, N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(3-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-butynyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(2-thienylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-(benzylamino)-1-[4-(benzyloxy)benzyl]-2-hydroxypropyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(cyclohexylmethyl)-2-hydroxypropyl3-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 2,3,5-trideoxy-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-methoxybenzyl)amino]-1-S-phenyl-1-thio-D-erythro-pentitol, N¹-[(1S,2R)-3-(benzylamino)-1-(3-furylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(4-fluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(2-fiirylmethyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-methylbutyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(4-hydroxybenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-butynyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-butynyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, 5-(benzylamino)-2,3,5-trideoxy-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-1-S-phenyl-1-thio-D-erythro-pentitol, N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N I -[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(4-hydroxybenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-methylbutyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl3-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(3-furylmethyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-((1S)-1-{(1R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-1-(4-fluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-(benzylamino)-1-(2-flurylmethyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(1-naphthylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N-{(S,2R)-3-(benzylamino)-1-[4-(benzyloxy)benzyl]-2-hydroxypropyl -5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-(benzylamino)-2-hydroxy-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S)-1-[(1R)-2-(benzylamino)-1-hydroxyethyl]-3-butynyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(cyclohexylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-((1S)-1-{(I R)-1-hydroxy-2-[(3-methoxybenzyl)amino]ethyl}-3-methylbutyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1 44-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-[3-(hydroxymethyl)benzyl]-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-[3-(hydroxymethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-[3-(hydroxymethyl)benzyl]-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-[4-(hydroxymethyl)benzyl]-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N 1-{(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-[4-(hydroxymethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, Nl¹-{(1S,2R)-2-hydroxy-1-[4-(hydroxymethyl)benzyl]-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-ethylbenzyl)amino]-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro-5-hydroxybenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, . N-{(1S,2R)-1-[3-(benzyloxy)-5-fluorobenzyll-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[3-(benzyloxy)-5-fluorobenzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N 1-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(l -naphthylmethyl)propyllpropanamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1-naphthylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}propanamide, N¹-{(1S,2R)-1-(4-fluorobenzyl)-2-hydroxy-3-[(3-rnethoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, ³-[(dipropylamino)sulfonyl]-N-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzy1)-3-[(³-rnethoxybenzyl)amino]propyl}propanamide, N¹-{(1S,2R)-2-hydroxy-1-(4-hydroxybenzyl)-3-[(3-mrethoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-mnethoxybenzyl)amino]propyl}propanamide, N¹-{(1S,2R)-1-(2-furylmethyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, ³-[(dipropylamino)sulfonyl]-N-{(1S,2R)-1-(²-furylmethyl)-2-hydroxy-3-[(3-nmethoxybenzyl)amino]propyl}propanamide, Ni -{(1S,2R)-1-(3-furylmethyl)-2-hydroxy-3-[(3-nmethoxybenzyl)amino]propyl}-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-rmethoxybenzyl)amino]-1-(²-thienylmethyl)propyljpropanamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-thienylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide, 3-[(dipropylamino)sulfonyl]-N-[(1S,2R)-2-hydroxy-3-[(3-mnethoxybenzyl)amino]-1-(³-thienylmethyl)propyl]propanamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-mthoxybenzyl)amino]-1-(2-thienylmethyl)propyl]-N⁵,N⁵-dipropylpentanediamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-3-{[(2R)-1-ethylpyrrolidinyl]carbonyl}-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-mnethoxybenzyl)amino]propyl}-3-{[(2S)-1-ethylpyrrolidinyl]carbonyl}-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-ethyl-1H-imidazol-2-yl)carbonyl]-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[(1-ethyl-4-methyl-1H-imidazol-5-yl)carbonyl]-5-methylbenzamide, N¹-((1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-2-{1-[(3-methoxybenzyl)amino] cyclopropyl}ethyl)-5-methyl-N³,N³-dipropylisophthalamide, N I-((1S,2S)-1-(3,5-difluorobenzyl)-2-{ I -[(³-ethylbenzyl)amino]cyclopropyl}-2-hydroxyethyl)-5-methyl-N³,N³-dipropylisophthalamide, (1R,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl3-N²,N²-dipropyl-1,²,³-cyclopropanetricarboxamide, (1R,2R,3R)-N¹-1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-phenyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-phenyl-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,²,³-cyclopropanetricarboxamide, (1R,2R,3S)-3-(2-amino-2-oxoethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3R)-3-(2-amino-2-oxoethyl)-N 1-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N²,N²-dipropyl-1,2-cyclopropanedicarboxamide, (1R,2R,3S)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-methylcyclopropanecarboxamide, (1R,2R,3R)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-methylcyclopropanecarboxamide, (1S,2R,3R)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-phenylcyclopropanecarboxamide, (1S,2R,3S)-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[2-(dipropylamino)-2-oxoethyl]-3-phenylcyclopropanecarboxamide, (1S,2R,3R)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[2-(dipropylamino)-2-oxoethyl]-1,2-cyclopropanedicarboxamide, (1S,2R,3S)-N¹-{(1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[2-(dipropylamino)-2-oxoethyl]-1,2-cyclopropanedicarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-, [(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-{methyl[(trifluoromethyl)sulfonyl]amino}-N³,N³-dipropylisophthalamide, N¹-{(S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-{methyl[(trifluoromethyl)sulfonyl]amino}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-5-{propyl[(trifluoromethyl)sulfonyl]amino}isophthalamide, N^(I)-{1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluoroberizyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-3-[(dipropylamino)sulfonyl]propanamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-³-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[³-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-3-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-thiazol-5-yl)methyl]amino}-²-hydroxypropyl)-3-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-thiazol-5-yl)methyl]amino}propyl)-³-[(dipropylamino)sulfonyl]propanamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-5-=isoxazolyl)methyl]amino}propyl)-3-[(dipropylaminonsulfonyllpropanamide, N-[(1S,2R)-3-[(3-cyclopropylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-3-[(dipropylamino)sulfonyl]propanamide, N¹-[(1S,2R)-3-[(3-cyclopropylbenzyl)amino]—(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1,3-thiazol-2-yl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophffialamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1,3-oxazol-2-yl)benzyljamino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,²R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-(aminosulfonyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-acetylbenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-(methylsulfonyl)-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[3-(diethylamino)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(4-morpholinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-piperazinyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[3-(aminosulfonyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({3-[(dimethylamino)sulfonyl]benzyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-{[3-(1-*—piperidinylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-i.- (methylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(isopropylsulfonyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-{[3-(aminocarbonyl)benzyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({3-[(dimethylamino)carbonyl]benzyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-cyanobenzyl)amino]-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, 3-({[(2R,3S)4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)phenylcarbamate, 3-({[(2R,3S)-4-(3,5-difluorophenyl)-3-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-2-hydroxybutyl]amino}methyl)phenyl dimethylcarbamate, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-propynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-methyl-1-butynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(2-propynyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide,, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(5-isobutyl-1,3,4-oxadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(5-ethyl-1,3,4-thiadiazol-2-yl) methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(5-isobutyl-1,3,4-thiadiazol-2-yl) methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(3-ethyl-1,2,4-thiadiazol-5-yl) methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-isobutyl-1,2,4-thiadiazol-5-yl) methyl]amino}propyl)-5-methyl-N³,N3-dipropylisophthalamide , N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(3-isobutyl-1,2,4-oxadiazol-5-yl) methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N-((S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(3-ethyl-16,2,4-oxadiazol-5-yl) methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, Nl1-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-1,3-oxazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-1,3-oxazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N3-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isobutyl-1,3,4-oxadiazol-2-yl)methyleamino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, 6s4 N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isobutyl-1,3,4-thiadiazol-2-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N I-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-1,3,4-thiadiazol-2-yl)methyl] amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{f [(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-. thiadiazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(3-isobutyl-1,2,4-. !n oxadiazol-5-yl)methyl]amino}propyl)-5mty-3N3-dipropylisophthalamide, N¹-((S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-2H-tetraazol-5-yl)methylaaminol-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isobutyl-2H-tetraazol-5-yl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethyl-4-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(2-isopropyl-4-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((S,2R)-1-(3,5-difluorobenzyl)-3-{[(2-ethynyl4-pyrimidinyl)methyl]amino-3-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-4-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[6-(dimethylamino)-4-pyrimidinyl]methylyamino)-2-hydroxypropyl]-5-methyl-N3,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[2-(dimethylamino)-4-pyrimidinyl]methyl}amino)-2-hydroxypropylJ-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({[4-(dimethylamino)-2-pyrimidinyl]methyl}amino)-2-hydroxypropyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4-isopropyl-2-pyrimidinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4-ethyl-2-pyrimidinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(5-ethyl-3-pyridazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(5-isopropyl-3-pyridazinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[3-(1-propynyl)benzyl]amino}propyl)-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-4-pyridazinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(6-ethyl-4-pyridazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(6-ethyl-2-pyrazinyl)methyl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N⁵,N⁵-dipropyl-3,5-pyridinedicarboxamide, N¹-((S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(6-isopropyl-2-pyrazinyl)methyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3,4,5-trifluorobenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-2-hydroxy-1-(3,4,5-trifluorobenzyl)-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-2-hydroxy-1-(2,3,5,6-tetrafluorobenzyl)-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2,3,5,6-tetrafluorobenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(1R,2S)-2-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl]amino}propyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1R,2S)-6-ethyl-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-2-hydroxypropyl)-5-methyl-N³,N³-dipropylisophthalamide, N¹-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(1R,2S)-6-ethyl-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}-2-hydroxypropyl)-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(1H-indol-5-ylmethyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(1H-indol-5-ylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N I -[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(3-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{((1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1 3-(trifluoromethyl)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethyl)benzyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-pyridinylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-pyridinylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-1{(1S,2R)-1-[3-fluoro-5-(trifluoromethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[3-fluoro-5-(trifluoromethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethoxy)benzyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[3-(trifluoromethoxy)benzyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(3-hydroxybenzyl)-3-[(3-methoxybenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(3-hydroxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(4-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(4-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-fluoro-3-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-fluoro-3-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-chlorobenzy1)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(3-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{((1S,2R)-2-hydroxy-1-(3-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N¹-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N-{(1S,2R)-2-hydroxy-1-(4-methoxybenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-chloro-5-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methy -N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-chloro-5-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(4-chloro-3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(4-chloro-3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3,5-dichlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino}propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-dichlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[4-(dimethylamino)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(f1S,2R)-1-[4-(dimethylamino)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N 1-{(1S,2R)-1-(3-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-chlorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-1-(4-isopropylbenzyl)-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-1-(4-isopropylbenzyl)-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(6-methoxy-2-pyridinyl)methyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(6-methoxy-2-pyridinyl)methyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(5-methyl-2-pyridinyl)methyl]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-[(5-methyl-2-pyridinyl)methyl]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-fluoro4-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro4-methylbenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3-fluoro-4-methoxybenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-methoxy-5-methylbenzyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(2-methoxy-5-methylbenzyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1,3-thiazol-2-ylmethyl)propyl]-5-methyl-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-2-hydroxy-3-[(3-methoxybenzyl)amino]-1-(1,3-thiazol-2-ylmethyl)propyl]-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N¹-{(1S,2R)-1-[(5-chloro-2-thienyl)methyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-[(5-chloro-2-thienyl)methyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N³,N³-dipropyl-1,3,5-benzenetricarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(propylsulfonyl)amino]-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl})4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(propylsulfonyl)aminol-1,3-thiazole4-carboxamide, N-{(1S,2R)-1-benzyl-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)-1-methylethyl]amino}-2-hydroxypropyl)-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)4-hydroxy-3-(1-pyrrolidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N— ((1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethynylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-piperidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-piperidinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-I ,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-4-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(4-morpholinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(ethylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino}propyl]-4-[(ethylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(4-morpholinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-[(propylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}) —[(methylsulfonyl)amino]-1,3-thiazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-3-(1-piperazinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}4-[(methylsulfonyl)amino]1-,3-thiazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁵-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-3-(1-piperazinylcarbonyl)benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N⁴-{(S ,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4,5-dicarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methyl-2-[(methylsulfonyl)amino]-1,3-oxazole-5-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N 1 {(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-methyl-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-methyl-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl3-N³-ethyl4-hydroxyisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-1,3-oxazole-2-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3[(3-iodobenzyl)amino]propyl}-2-[(ethylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-3-isoxazolecarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³-ethyl-4-hydroxyisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-[(methylsulfonyl)amino]-3-isoxazolecarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-[(methylsulfonyl)amino]-5-isoxazolecarboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-N³-ethyl4-hydroxyisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(methylsulfonyl)amino]-5-isoxazolecarboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(propylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-(hydroxymethyl)-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-4-hydroxyisophthalamide, 5-cyclopropyl-N-{(1S,2R)-1-(3,5difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(propylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-5-isopropyl-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxyisophthalamide, N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-2-[(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-{(1S,2R)-1-(3, 5-dfluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-2-[(propylsulfonyl)amino]-1,3-oxazole4-carboxamide, N-[(1S,²R)-3-(cyclopropylamino)-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-2-[(methylsulfonyl)amino]-l ,3-oxazole-4-carboxamide, N-[(1S,2R)-3-[(3-ethylbenzyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propyl]-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N I -{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁴-hydroxy-N³-isobutylisophthalamide, 2-{[(cyclopropylmethyl)sulfonyl]amino}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-³-[(³-ethylbenzyl)amino]-2-hydroxypropyl}-1,³-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-isobutyl-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(isobutylsulfonyl)amino]-1,³-oxazole4-carboxamide, N³-(cyclopropylmethyl)-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}4-hydroxy-N³-methylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-2-[(isobutylsulfonyl)amino]-1,³-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-hydroxy-N³-methyl-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(isobutylsulfonyl)amino]-1,3-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl) 4-hydroxy-N³-methyl-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(phenylsulfonyl)amino]-1,3-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N3-ethyl4-hydroxy-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-{[(4-methylphenyl)sulfonyl]amino -1,3-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-ethyl4-hydroxy-N³-propylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-{[(4-methylphenyl)sulfonyl]amino}-1,³-oxazole4-carboxamide, N-{(1S,2R)-1-(3,5-difluorobenzy1)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-²-[(phenylsulfonyl)amino]-1,³-oxazole-4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino-3-2-hydroxypropyl}-4-hydroxy-N³, N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-²-[methyl(methylsulfonyl)amino]-1,³-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4-hydroxy-N³, N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-²-[methyl(methylsulfonyl)amino]-1,3-oxazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl})4-hydroxy-N³, N³-dipropylisophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-2-[(methylsulfonyl)amino]-1,³-tbiazole4-carboxamide, N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-²-[(methylsulfonyl)amino]-1,3-thiazole4-carboxamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(ethylsulfonyl)amino]-N³,N³dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³⁴ipropyl-5-[(propylsulfonyl)amino]isophthalamide, N^(l)-{(S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(isopropylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁵-[(isobutylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(thien-2-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁵-[(²-furylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(1,³-thiazol-5-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzy1)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(1,³-oxazol-5-ylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[(1,3-oxazol-4-ylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-[(1,³-thiazol-4-ylsulfonyl)amino]isophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-{[(1-methyl-1H-imidazol-4-yl)sulfonyl] amino}-N³,N³-dipropylisophthalamide, N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-⁵-[(phenylsulfonyl)amino]-N³,N³-dipropylisophthalamide, 5-{[(5-cyanopyridin-2-yl)sulfonyl]amino}-N¹-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxyproy}N3,3 dipropylisophthalamide, N¹-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N³,N³-dipropyl-5-({[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}amino)isophthalamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-lhydroxypropyl}-3-{[(1-methyl-1H-imidazol4-yl)sulfonyl]amino}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-({[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}amino)benzamide, 3-{[(5-cyanopyridin-2-yl)sulfonyl]amino}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-³-[(³-ethylbenzyl)amino]-2-hydroxypropyl}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(phenylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(methylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(³,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(ethylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(propylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(isobutylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(isopropylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl3-3-{[(1-ethylpropyl)sulfonyl]amino}benzamide, 3-[(cyclohexylsulfonyl)amino]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(1-propylbutyl)sulfonyl]amino}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(thien-2-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(2-furylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-³-[(isoxazol-5-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(isoxazol-3-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3-furylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(thien-3-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-3-[(1,3-thiazol4-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,3-thiazol-5-ylsulfonyl)amino]benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(1,3-thiazol-2-ylsulfonyl)amino]benzamide, N¹-[(1S,2R)-1-(³,5-difluorobenzyl)-2-hydroxy-3-(isopentylamino)propyl]-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-N³,N³-dipropyl-5-{[(trifluoromethyl)sulfonyl]amino}isophthalamide, N¹-[(1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropyl]-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-[(1S,2R)-1-(3,5-difluorobenzy1)-2-hydroxy-3-(isopentylamino)propyl]-5-[(methylsulfonyl)amino]-N³,N³-dipropylisophthalamide, N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isophthalamide, N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylisophthalamide, 5-bromo-N¹-(tert-butyl)-N³-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isophthalamide, 3-tert-butoxy-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide, 3-tert-butoxy-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide, N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-(trifluoromethoxy)benzamide, and N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(trifluoromethoxy)benzamide.
 183. A pharmaceutical composition which comprises a substituted amine of formula (X)

where R₁ is: (I) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, C₁-C₇ alkyl (optionally substituted with C₁-C₃ alkyl and C₁-C₃ alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (III) —CH₂—CH₂—S(O)₀₋₂—(C₁-C₆ alkyl), (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C]-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C—C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (VI) —(CH₂)_(n-1)—(R_(1-aryl)) where n₁ is zero or one and where R_(1-aryl) is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three, or four of the following substituents on the aryl ring: (A) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C≡N, —CF₃, C₁-C₃ alkoxy, (B) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C—C₆ alkyl, (C) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R. b are —H or C₁-C₆ alkyl, (D) —F, Cl, —Br or —I, (F) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (G) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (H) —OH, (I) —C≡N, (J) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (K) —CO—(C₁-C₄ alkyl), (L) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (M) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (N) —SO₂—(C₁-C₄ alkyl), (VII) —(CH₂)_(n1)—(R_(1-heteroaryl)) where n₁ is as defined above and where R_(1-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyi, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cirnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, where the R_(1-heteroaryl) group is bonded to —(CH₂)_(n1)— by any ring atom of the parent R_(1-heteroaryl) group substituted by hydrogen such that the new bond to the R_(1-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of: —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (14) —SO₂—(C₁-C₄ alkyl), with the proviso that when n₁ is zero R_(1-heteroaryl) is not bonded to the carbon chain by nitrogen, or (VIII) —(CH₂)_(n-1)—(R_(1-heterocycle)) where n₁ is as defined above and R_(1-heterocycle) is selected from the group consisting of: morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, and oxazolidinonyl, dihydropyrazolyl dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl dihydrofuryl dihydropyranyl tetrahydrothienyl S-oxide tetrahydrothienyl S,S-dioxide homothiomorpholinyl S-oxide where the R_(1-heterocycle) group is bonded by any atom of the parent R_(1-heterocycle) group substituted by hydrogen such that the new bond to the R_(1-heterocycle) group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three, or four: (1) C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (3) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (4) —F, Cl, —Br or —I, (5) C₁-C₆ alkoxy, (6) —C₁-C₆ alkoxy optionally substituted with one, two, or three of —F, (7) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined below, (8) —OH, (9) —C≡N, (10) C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, -C_N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (11) —CO—(C₁-C₄ alkyl), (12) —SO₂—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (13) —CO—NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (14) —SO₂—(C₁-C₄ alkyl), or (15) ═O, with the proviso that when n₁ is zero R_(1-heterocycle) is not bonded to the carbon chain by nitrogen; where R₂ is: (I) —H, (II) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀₋₄—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-hetroaayl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, (V) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl; where R₃ is: (I) —H, (II) C₁-C₆ allyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CH₂)₀4—R₂₋₁ where R₂₋₁ is R_(1-aryl) or R_(1-heteroaryl) where R_(1-aryl) and R_(1-heteroaryl) are as defined above; (IV) C₂-C₆ alkenyl with one or two double bonds, (V) C₂-C₆ alkynyl with one or two triple bonds, or (VI) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are —H or C₁-C₆ alkyl, and where R₂ and R₃ are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)-, where R_(N-2) is as defined below; where R_(N) is: (I) R_(N-1)—X_(N)— where X_(N) is selected from the group consisting of: (A) —CO—, (B) —SO₂—, (C) —(CR′R″)₁₋₆ where R′ and R″ are the same or different and are —H or C₁-C₄ alkyl, (D) —CO—(CR′R″)₁₋₆—X_(N-1) where X_(N-1) is selected from the group consisting of —O—, —S— and —NR′— and where R′ and R″ are as defined above, and (E) a single bond; where R_(N-1) is selected from the group consisting of: (A) R_(N-aryl) where R_(N-aryl) is phenyl, 1-naphthyl, 2-naphthyl, tetralinyl, indanyl, dihydronaphthyl or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, optionally substituted with one, two or three of the following substituents which can be the same or different and are: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2) —OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I, (5) —CO—OH, (6) —C≡N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄—CO—(C₂-C]₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄—CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, and (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CU2)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or RNS5)—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄—N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄—O—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (B) —R_(N-heteroaryl) where R_(N-heteroaryl) is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, and pyridinyl-N-oxide, tetrahydroquinolinyl dihydroquinolinyl dihydroquinolinonyl dihydroisoquinolinonyl dihydrocoumarinyl dihydroisocoumarinyl isoindolinonyl benzodioxanyl benzoxazolinonyl pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide , benzothiopyranyl S,S-dioxide, where the R_(N-heteroaryl) group is bonded by any atom of the parent R_(N-heteroaryl) group substituted by hydrogen such that the new bond to the R_(N-heteroaryl) group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four of: (1) C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (2)—OH, (3) —NO₂, (4) —F, —Cl, —Br, or —I (5) —CO—OH, (6) —C_N, (7) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are selected from the group consisting of: (a) —H, (b) —C₁-C₆ alkyl optionally substituted with one substitutent selected from the group consisting of: (i) —OH, and (ii) —NH₂, (c) —C₁-C₆ alkyl optionally substituted with one to three —F, —Cl, —Br, or —I, (d) —C₃-C₇ cycloalkyl, (e) —(C₁-C₂ alkyl)—(C₃-C₇ cycloalkyl), (f) —(C₁-C₆ alkyl)—O—(C₁-C₃ alkyl), (g) —C₂-C₆ alkenyl with one or two double bonds, (h) —C₂-C₆ alkynyl with one or two triple bonds, (i) —C₁-C₆ alkyl chain with one double bond and one triple bond, (j) —R_(1-aryl) where R_(1-aryl) is as defined above, and (k) —R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (8) —(CH₂)₀₋₄—CO—(C₁-C₁₂ alkyl), (9) —(CH₂)₀₋₄—CO—(C₂-C₁₂ alkenyl with one, two or three double bonds), (10) —(CH₂)₀₋₄CO—(C₂-C₁₂ alkynyl with one, two or three triple bonds), (11) —(CH₂)₀₋₄—CO—(C₃-C₇ cycloalkyl), (12) —(CH₂)₀₋₄CO—R_(1-aryl) where R_(1-aryl) is as defined above, (13) —(CH₂)₀₋₄—CO—R_(1-heteroaryl) where R_(1-heteroaryl) is as defined above, (14) —(CH₂)₀₋₄—CO—R_(1-heterocycle) where R_(1-heterocycle) is as defined above, (15) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with one, two, three, or four of: C₁-C₆ alkyl, (16) —(CH₂)₀₋₄—CO—O—R_(N-5) where R_(N-5) is selected from the group consisting of: (a) C₁-C₆ alkyl, (b) —(CH₂)₀₋₂—(R_(1-aryl)) where R_(1-aryl) is as defined above, (c) C₂-C₆ alkenyl containing one or two double bonds, (d) C₂-C₆ alkynyl containing one or two triple bonds, (e) C₃-C₇ cycloalkyl, (f) —(CH₂)₀₋₂—(R_(1-heteroaryl)) where R_(1-heteroaryl) is as defined above, (17) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are as defined above, (18) —(CH₂)₀₋₄—SO—(C₁-C₈ alkyl), (19) —(CH₂)₀₋₄—SO₂—(C₁-C₁₂ alkyl), (20) —(CH₂)₀₋₄—SO₂—(C₃-C₇ cycloalkyl), (21) —(CH₂)₀₋₄—N(H or R_(N-5))—CO—O—R_(N-5) where R_(N-5) can be the same or different and is as defined above, (22) —(CH₂)₀₋₄—N(H or R_(N-5)) —CO—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (23) —(CH₂)₀₋₄-N—CS—N(R_(N-5))₂, where R_(N-5) can be the same or different and is as defined above, (24) —(CH₂)₀₋₄—N(—H or R_(N-5))—CO—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as defined above, (25) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) can be the same or different and are as defined above, (26) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (27) —(CH₂)₀₋₄—O—CO—(C₁-C₆ alkyl), (28) —(CH₂)₀₋₄₀—P(O)—(OR_(N-aryl-1))₂ where R_(N-aryl-1) is —H or C₁-C₄ alkyl, (29) —(CH₂)₀₋₄—O—CO—N(R_(N-5))₂ where R_(N-5) is as defined above, (30) —(CH₂)₀₋₄—O—CS—N(R_(N-5))₂ where R_(N-5) is as defined above, (31) —(CH₂)₀₋₄—O—(R_(N-5))₂ where R_(N-5) is as defined above, (32) —(CH₂)₀₋₄—O—(R_(N-5))₂—COOH where R_(N-5) is as defined above, (33) —(CH₂)₀₋₄—S—(R_(N-5))₂ where R_(N-5) is as defined above, (34) —(CH₂)₀₋₄—O—(C₁-C₆ alkyl optionally substituted with one, two, three, four, or five of: —F), (35) C₃-C₇ cycloalkyl, (36) C₂-C₆ alkenyl with one or two double bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (37) C₂-C₆ alkynyl with one or two triple bonds optionally substituted with C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, -C-=N, —CF₃, C₁-C₃ alkoxy, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, or (38) —(CH₂)₀₋₄—N(—H or R_(N-5))—SO₂—R_(N-2) where R_(N-5) and R_(N-2) can be the same or different and are as described above, or (39) —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, (C) R_(N-aryl)—W—R_(N-aryl), where R_(N-aryl) is defined as above, (D) R_(N-aryl)—W—R_(N-heteroaryl) where R_(N-aryl) and R_(N-heteroaryl) are as defined above, (E) R_(N-aryl)—W—R_(N-1-heterocycle) where R_(N-heterocycle) is defined as R_(1-heterocycle), is defined above, (F) R_(N-heteroaryl)—W—R_(N-aryl), where R_(N-aryl) and R_(n-heteroaryl) are as defined above, (G) R_(N-heteroaryl)—W—R_(N-heteroaryl), where R_(N-heteroaryl) is as defined above, (H) R_(N-heteroaryl)—W—R_(N-1-heterocycle), where R_(N-1-heterocycle) is as defined as R_(1-heterocycle) is as defined above, and where R_(N-heteroaryl) is as defined above, (I) R_(N-heterocycle)—W—R_(N-aryl), where R_(N-heterocycle) is as defined as R_(1-heterocycle) is defined and where R_(N-aryl) are as defined above, (J) R_(N-heterocycle)—W—R_(N-heteroaryl), where R_(N-heterocycle) is as defined as R_(1-heterocycle) as defined above and R_(N-heteroaryl) are as defined above, and (K) R_(N-heterocycle)—W—R_(N-1-heterocycle), where R_(N-heterocycle) and R_(N-heteroaryl) are as defined above, where W is (21) —(CH₂)₀₋₄—, (22) —O—, (23)—S(O)₀₋₂—, (24) —N(R_(N-5))— where R_(N-5) is as defined above, or (25) —CO—, (II) —CO—(C₁-C₁₀ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of. (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl (III) —CO—(C₁-C₆ alkyl)—O—(C₁-C₆ alkyl) where alkyl isoptionally substituted with one, two, or three substitutents selected from the group consisting of: (A)—OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -ø, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where the R_(N-8) s are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, —Cl, (IV) —CO—(C₁-C₆ alkyl)—S—(C₁-C₆ alkyl) where alkyl is optionally substituted with one, two, or three substitutents selected from the group consisting of: (A) —OH, (B) —C₁-C₆ alkoxy, (C) —C₁-C₆ thioalkoxy, (D) —CO—O—R_(N-8) where R_(N-8) is as defined above, (E) —CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —CO—R_(N-4) where R_(N-4) is as defined above, (G) —SO₂—(C₁-C₈ alkyl), (H) —SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), (R) —F, or —Cl, (V) —CO—CH(—CH₂)₀₋₂—O—R_(N-10)) —(CH₂)₀₋₂—R_(N-aryl)/R_(N-heteroalyl)) where R_(N-aryl) and R_(N-heteroaryl) are as defined above, where R_(N-10) is selected from the group consisting of: (A) —H, (B) C₁-C₆ alkyl, (C) C₃-C₇ cycloalkyl, (D) C₂-C₆ alkenyl with one double bond, (E) C₂-C₆ alkynyl with one triple bond, (F) R_(1-aryl) where R_(1-aryl) is as defined above, and (G) R_(N-heteroaryl) where R_(N-heteroaryl) is as defined above, or (VI) —CO—(C₃-C₈ cycloalkyl) where alkyl is optionally substituted with one or two substitutents selected from the group consisting of: (A) —(CH₂)₀₋₄—OH, (B) —(CH₂)₀₋₄-C₁-C₆ alkoxy, (C) —(CH₂)₀₋₄-C₁-C₆ thioalkoxy, (D) —(CH₂)₀₋₄—CO—O—R_(N-8) where R_(N-8) is —H, C₁-C₆ alkyl or -phenyl, (E) —(CH₂)₀₋₄—CO—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (F) —(CH₂)₀₋₄—CO—R_(N-4) where R_(N-4) is as defined above, (G) —(CH₂)₀₋₄—SO₂—(C₁-C₈ alkyl), (H) —(CH₂)₀₋₄—SO₂—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (I) —(CH₂)₀₋₄—NH—CO—(C₁-C₆ alkyl), (J) —NH—CO—O—R_(N-8) where R_(N-8) is as defined above, (K) —(CH₂)₀₋₄—NR_(N-2)R_(N-3) where R_(N-2) and R_(N-3) are the same or different and are as defined above, (L) —(CH₂)₀₋₄—R_(N-4) where R_(N-4) is as defined above, (M) —O—CO—(C₁-C₆ alkyl), (N) —O—CO—NR_(N-8)R_(N-8) where R_(N-8) are the same or different and are as defined above, (O) —O—(C₁-C₅ alkyl)—COOH, (P) —O—(C₁-C₆ alkyl optionally substitued with one, two, or three of: —F, —Cl, —Br, or —I), (Q) —NH—SO₂—(C₁-C₆ alkyl), and (R) —F, or —Cl, where R_(C) is: (I) —C₁-C₁₀ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —OC═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —S(═O)₀₋₂ R_(1-a) where R_(1-a) is as defined above, —NR_(1-a)C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, —C═O NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, and —S(═O)₂ NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (II) —(CH₂)₀₋₃—(C₃-C₈) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —CO—OH, —CO-O—(C₁-C₄ alkyl), and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (III) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl) where R_(C-x) and R_(C-y) are —H, C₁-C₄ alkyl optionally substituted with one or two —OH, C₁-C₄ alkoxy optionally substituted with one, two, or three of: —F, —(CH₂)₀₋₄—C₃-C₇ cycloalkyl, C₂-C₆ alkenyl containing one or two double bonds, C₂-C₆ alkynyl contianing one or two triple bonds, phenyl-, and where R_(C-x) and R_(C-y) are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six, or seven carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of —O—, —S—, —SO₂—, and —NR_(N-2)— and R_(C-aryl) is the same as R_(N-aryl); (IV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl) where R_(C-heteroaryl) is the same as R_(N-heteroaryl) and R_(C-x) and R_(C-y) are as defined above, (V) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-aryl) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heteroaryl) where R_(C-aryl), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (VII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-aryl) where R_(C-heteroaryl) R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (VI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heteroaryl) where R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (IX) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-aryl)—R_(C-heterocycle) where R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, and R_(C-heterocycle) is the same as R_(N-hetetocycle), (X) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heteroaryl)—R_(C-heterocycle) where R_(C-heteroaryl), R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XI) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-aryl) where R_(C-heterocycle), R_(C-aryl), R_(C-x) and R_(C-y) are as defined above, (XII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heteroaryl) where R_(C-heterocycle), R_(C-heteroaryl), R_(C-x) and R_(C-y) are as defined above, (XIII) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle)—R_(C-heterocycle) where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XIV) —(CR_(C-x)R_(C-y))₀₋₄—R_(C-heterocycle) where R_(C-heterocycle), R_(C-x) and R_(C-y) are as defined above, (XV) —[C(R_(C-1))(R_(C-2))]₁₋₃—CO—N—(R_(C-3))₂ where R_(C-1) and R_(C-2) are the same or different and are selected from the group consisting of: (A) —H, (B) —C₁-C₆ alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, -CaN, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₁₋₂—S(O)₀₋₂—(C₁-C₆ alkyl), (F) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (G) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as defined for R_(1-aryl), (H) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (I) —(C₁-C₄ alkyl)—R_(C-heterocycie) where R_(C-heterocycle) is as defined above, (J) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (K) —R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (M) —(CH₂)₁₋₄—R_(C-4)—(CH₂)₀₋₄—R_(C′-aryl) where R_(C-4) is —O—, —S— or —NR_(C-5)— where R_(C-5) is C₁-C₆ alkyl, and where R_(C′-aryl) is as defined above, (N) —(CH₂)₁₋₄—R_(C-4)—CH₂)₀₋₄—R_(C-heteroaryl) where R_(C-4) and R_(C-heteroaryl) are as defined above, and (O)—R_(C′-aryl) where R_(C′-aryl) is as defined above, and where R_(C-3) is the same or different and is: (A) —H, (B) —C₁-C₆ alkyl optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (C) C₂-C₆ alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (D) C₂-C₆ alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (E) —(CH₂)₀₋₄-C₃-C₇ cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (F) —R_(C′-aryl) where R_(C′-aryl) is as defined above, (G) —R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, (H) —R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (I) —(C₁-C₄ alkyl)—R_(C′-aryl) where R_(C′-aryl) is as defined above, (J) —(C₁-C₄ alkyl)—R_(C-heteroaryl) where R_(C-heteroaryl) is as defined above, or (K) —(C₁-C₄ alkyl)—R_(C-heterocycle) where R_(C-heterocycle) is as defined above, (XVI) —CH(R_(C-aryl))₂ where R_(C-aryl) are the same or different and are as defined above, (XVII) —CH(R_(C-heteroaryl))₂ where R_(C-heteroaryl) are the same or different and are as defined above, (XVIII) —CH(R_(C-aryl))(R_(C-heteroaryl)) where R_(C-aryl) and R_(C-heteroaryl) are as defined above, (XIX)-cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) where R_(C-aryl) or R_(C-heteroaryl) or R_(C-heterocycle) are as defined above where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR_(N-5), O, or S(═O)₀₋₂, and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two —C₁-C₃ alkyl, —F, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, ═O, or —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XX) C₂-Clo alkenyl containing one or two double bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) C₂-C₁₀ alkynyl containing one or two triple bonds optionally substituted with one, two or three substituents selected from the group consisting of C₁-C₃ alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF₃, C₁-C₆ alkoxy, —O-phenyl, and —NR_(1-a)R_(1-b) where R_(1-a) and R_(1-b) are as defined above, (XXI) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-aryl) where R_(C-aryl) is as defined above and R_(C-6) is —(CH₂)₀₋₆—OH, (XXII) —(CH₂)₀₋₁—CHR_(C-6)—(CH₂)₀₋₁—R_(C-heteroaryl) where R_(C-heteroaryl) and R_(C-6) is as defined above, (XXIII) —CH(—R_(C-aryl) or R_(C-heteroaryl))—CO—O(C₁-C₄ alkyl) where R_(C-aryl) and R_(C-heteroaryl) are as defined above, (XXIV) —CH(—CH₂—OH)—CH(—OH)-phenyl-NO₂, (XXV) (C₁-C₆ alkyl)—O—(C₁-C₆ alkyl)—OH, (XXVII) —CH₂—NH—CH₂—CH(—O—CH₂—CH₃)₂, (XXVIII) —H, or (XXIX) —(CH₂)₀₋₆—C(═NR_(1-a))(NR_(1-a)R_(1-b)) where R_(1-a) and R_(1-b) are as defined above; or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable inert carriers.
 184. A method for inhibiting beta-secretase activity, comprising exposing said beta-secretase to an effective inhibitory amount of a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 185. The method of claim 184, wherein said beta-secretase is exposed to said compound in vitro.
 186. The method of claim 184, wherein said beta-secretase is exposed to said compound in a cell.
 187. The method of claim 186, wherein said cell is in an animal.
 188. The method of claim 187, wherein said animal is a human.
 189. A method for inhibiting cleavage of amyloid precursor protein (APP), in a reaction mixture, at a site between Met596 and Asp597, numbered for the APP-695 amino acid isotype; or at a corresponding site of an isotype or mutant thereof, comprising exposing said reaction mixture to an effective inhibitory amount of a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 190. The method of claim 189, wherein said cleavage site is between Met652 and Asp653, numbered for the APP-751 isotype; between Met 671 and Asp 672, numbered for the APP-770 isotype; between Leu596 and Asp597 of the APP-695 Swedish Mutation; between Leu652 and Asp653 of the APP-751 Swedish Mutation; or between Leu671 and Asp672 of the APP-770 Swedish Mutation.
 191. The method of claim 189, wherein said reaction mixture is exposed in vitro.
 192. The method of claim 189, wherein said reaction mixture is exposed in a cell.
 193. The method of claim 192, wherein said cell is an animal cell.
 194. The method of claim 193, wherein said cell is a human cell.
 195. A method for inhibiting production of amyloid beta peptide (A beta) in a cell, comprising administering to said cell an effective inhibitory amount of a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 196. The method of claim 195, wherein said administering is to an animal.
 197. The method of claim 196, wherein said administering is to a human.
 198. A method for inhibiting the production of beta-amyloid plaque in an animal, comprising administering to said animal an effective inhibitory amount of a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 199. The method of claim 198, wherein said animal is a human.
 200. A method for treating or preventing a disease characterized by beta-amyloid deposits in the brain comprising administering to a patient an effective therapeutic amount of a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 201. The method of claim 200, wherein said therapeutic amount is in the range of from about 0.1 to about 1000 mg/day.
 202. The method of claim 200, wherein said thereapeutic amount is in the range of from about 15 to about 1500 mg/day.
 203. The method of claim 202, wherein said thereapeutic amount is in the range of from about 1 to about 100 mg/day.
 204. The method of claim 203, wherein said thereapeutic amount is in the range of from about 5 to about 50 mg/day.
 205. The method of claim 200, wherein said disease is Alzheimer's disease.
 206. The method of claim 200, wherein said disease is Mild Cognitive Impairment, Down's Syndrome, or Hereditary Cerebral Hemmorrhage with Amyloidosis of the Dutch Type.
 207. A composition comprising beta-secretase complexed with a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 208. A method for producing a beta-secretase complex comprising: exposing beta-secretase, in a reaction mixture under conditions suitable for the production of said complex, to a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 209. The method of claim 208, where said exposing is in vitro.
 210. The method of claim 208, wherein said reaction mixture is a cell.
 211. A kit comprising component parts capable of being assembled, wherein at least one component part comprises, enclosed in a container, a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 212. The kit of claim 211, wherein said compound is lyophilized and at least one further component part comprises a diluent.
 213. A kit comprising a plurality of containers, each container comprising one or more unit dose of a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 214. The kit of claim 213, wherein each container is adapted for oral delivery and comprises a tablet, gel, or capsule.
 215. The kit of claim 214, wherein each container is adapted for parentemal delivery and comprises a depot product, syringe, ampoule, or vial.
 216. The kit of claim 214, wherein each container is adapted for topical delivery and comprises a patch, medipad, ointment, or cream.
 217. A kit comprising one or more therapeutic agent selected from the group consisting of an antioxidant, an anti-inflamatory, a gamma secretase inhibitor, a neurotrophic agent, an acetylcholinesterase inhibitor, a statin, an A beta peptide, and an anti-A beta antibody; and a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 218. A composition comprising an inert diluent or edible carrier; and a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 219. The composition of claim 218, wherein said carrier is an oil.
 220. A composition comprising a binder, excipient, disintegrating agent, lubricant, or gildant; and a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 221. A composition comprising a compound of formula (X)

where R₁, R₂, R₃, R_(N) and R_(C) are as defined in claim 1, or a pharmaceutically acceptable salt thereof, and where the compound is disposed in a cream, ointment, or patch. 